Medizinische Labordiagnostika EUROIMMUN AG

Product Catalogue

Diagnostics for the Determination of Autoantibodies, for Infectious Serology and Allergology

Indirect Immunofluorescence — ELISA — RIA — Westernblot EUROASSAY — EUROLINE — EUROPLUS Product Catalogue 2010 Product

IMMUN

2010 —1— EURO

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Table of Contents

EUROIMMUN – Company Profile ...... 3

Techniques for the Serological Investigation of Antibodies ...... 5 Indirect Immunofluorescence: An Easy and Modern Method ...... 6 BIOCHIP Mosaics™ ...... 9 The Indirect Immunofluorescence Test, Performed Using the TITERPLANE™ Technique...... 10 Recommended Serum Dilutions for Indirect Immunofluorescence ...... 12 Diagnostically Relevant Systemic Autoantibodies ...... 16 Organ-/Tissue-Specific Autoantibodies ...... 17 Antibodies for Infectious Serology ...... 18 Antibodies for Allergology ...... 19 EUROIMMUN Microplate ELISA ...... 18 ELISA Automation using the EUROIMMUN Analyzer I ...... 22 Incubating the Microplate ELISA ...... 23 EUROASSAY: Line Blots in TITERPLANE™Technique Format ...... 24 Incubating the EUROASSAY (TITERPLANE™Technique) ...... 25 The EUROLINE: A New Technique for Extensive Antibody Profiles ...... 26 EUROLINE Automation Using EUROBlotMaster and EUROLineScan ...... 27 Westernblots/EUROLINE-WB: Reliable Differentiation of Antibodies Present ...... 28 Incubating the EUROLINE/Westernblot/EUROLINE-WB ...... 29 EUROIMMUN Radioimmunoassays (RIA/IRMA) ...... 30

EUROIMMUN Products for the Determination of Autoantibodies ...... 31 Autoantibodies against Cell Nuclei (ANA) ...... 32 Autoantibodies against Double-Stranded DNA (dsDNA) ...... 35 Autoantibodies against CCP and Sa ...... 36 Autoantibodies against Mitochondria (AMA) ...... 37 Autoantibodies against Liver Antigens ...... 38 Autoantibodies against Thyroid Gland Antigens / Antigen Detections ...... 40 Autoantikörper against Antigens of the Skin ...... 41 Autoantibodies against Neuronal Antigens ...... 42 Autoantibodies against Islet Cell Antigens ...... 44 Autoantibodies against Parietal Cells (PCA) ...... 45 Autoantibodies against Granulocyte Cytoplasm (cANCA/pANCA) ...... 46 Antibodies against Endomysium and Gliadin ...... 48

EUROIMMUN Products for Infectious Serology ...... 49 Antibodies against Borrelia ...... 50 Antibodies against Epstein-Barr Virus (EBV) ...... 52 Antibodies against Helicobacter Pylori ...... 54 Antibodies against Herpes Simplex Virus (HSV) ...... 55 Antibodies against Chlamydia ...... 56 Antibodies against Emerging Viruses ...... 57 BIOCHIP Mosaics™ for Infectious Serology ...... 58 Additional Reagents for the Determination of Acute Infections ...... 60

EUROIMMUN Products for Allergology ...... 61

Order Information and Product Data ...... 64 Fluorescence-Labelled Antibodies: Fluorescein (FITC) for EUROIMMUN IIFT ...... 65 Controls for EUROIMMUN IIFT: Organ-Specific Autoantibodies ...... 66 Controls for EUROIMMUN IIFT: Systemic Autoantibodies ...... 68 Controls for EUROIMMUN IIFT: Infectious Serology ...... 70 Controls for EUROIMMUN IIFT: Determination of Further Antibodies ...... 76 Controls for EUROIMMUN Westernblots/EUROLINE-WB ...... 77 EUROASSAY for the Determination of Autoantibodies (Test Systems) ...... 79 EUROLINE for the Determination of Autoantibodies (Test Systems) ...... 80 EUROLINE for Infectious Serology (Test Systems) ...... 81 EUROLINE for Allergology (Test Systems) ...... 81 Westernblot/EUROLINE-WB for the Determination of Autoantibodies (Test Systems) ...... 83 Westernblot/EUROLINE-WB for Infectious Serology (Test Systems) ...... 84 Microplate ELISA for the Determination of Autoantibodies (Test Systems) ...... 86 Latex Agglutination tests for the Determination of Autoantibodies (Test Systems) ...... 89 EUROArray for Molecular Genetic Determinations (Test Systems) ...... 89 Radioimmunoassay (RIA) for the Determination of Autoantibodies / Autoantigens / Hormone Determination (Test Systems) ...... 89 Microplate ELISA for Infectious Serology (Test Systems) ...... 91 Microplate ELISA for the Determination of Antibodies against Other Antigens (Test Systems) ...... 95 Allercoat™ 6 System ...... 96 Diagnostics for Indirect Immunofluorescence: Organ-Specific Autoantibodies ...... 116 Diagnostics for Indirect Immunofluorescence: Systemic Autoantibodies ...... 126 Diagnostics for Indirect Immunofluorescence: Infectious Serology ...... 134 Diagnostics for Indirect Immunofluorescence: Other Antigens ...... 151 Further Reagents for EUROIMMUN IIFT ...... 151 Other Items for EUROIMMUN IIFT ...... 152 General Delivery Conditions ...... 153

Index ...... 154

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EUROIMMUN – COMPANY PROFILE

Company site Groß Grönau Company headquarters Lübeck

Company branch DassowCompany branch Rennersdorf Company branch Pegnitz

EUROIMMUN was founded in September 1987 and today has its headquarters in Lübeck, Germany. Branches are situated in Groß Grönau near Lübeck (Schleswig-Holstein), in Rennersdorf (Upper Lusatia, Saxony), Dassow (Mecklenburg-Western Pomerania) and in Pegnitz (Upper Franconia, Bavaria). Further EUROIMMUN subsidiaries can be found in Canada (Mississauga), China (Beijing, Hangzhou), Great Britain (Pontypool in Wales), Italy (Padua), Lebanon (Beirut), Poland (Wroclaw), Switzerland (Lucerne), Singapore, South Africa (Capetown), Turkey (Istanbul) and the USA (New Jersey). At present EUROIMMUN has 714 employees in Germany, 884 worldwide. The company is ISO-certified (EN ISO 9001:2008, EN ISO 13485:2003/ CMDCAS).

EUROIMMUN produces reagents for medical laboratory diagnostics. In the foreground are test systems for the determination of various antibodies in patient serum in the diagnosis of autoimmune diseases, infectious diseases and allergies.

The test methods employed are predominantly indirect immunofluorescence, microplate ELISA, various blot techniques (Westernblot, EUROASSAY, EUROLINE, EUROLINE-WB) and all molecular biology techniques. The company is based on worldwide-patented state-of-the-art production methods and microanalysis techniques and is one of the world’s leading manufacturers of medical laboratory diagnostics.

The BIOCHIPs are one of EUROIMMUN’s many inventions: paper-thin sheets of glass are coated with cells or tissue sections and then cut automatically into millimetre-sized fragments which are subsequently glued onto slides using a fully automated device. This BIOCHIP technology allows extreme miniaturization and standardization of immunbiochemical analyses. With BIOCHIP Mosaics™made from 30 or more different organ sections, cell substrates or defined antigens (EUROPLUS™) only minimum incubation efforts are necessary to obtain a detailed antibody profile.

In EUROIMMUN enzyme immunoassays (ELISA) defined antigens, purified using state-of-the-art biotechnological processes, are employed as the antigen substrate. Some of these antigens are synthesized in the company’s molecular biology laboratories. EUROIMMUN ELISA are characterized by their excellent stability, simple handling and short incubation times, and they are ideal for automated use. All reagents are delivered ready-to-use and are exchangeable between different lots. EUROIMMUN offers the largest and most differentiated arsenal of enzyme immunoassays worldwide for the diagnosis of autoimmune and infectious diseases. —3—

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The innovative procedures EUROASSAY and EUROLINE developed by EUROIMMUN follow the same test principle as the ELISA methods, with the use of the BIOCHIP technology. At EUROIMMUN purified antigens are printed in parallel lines at defined positions on membrane strips. Following incubation, users can evaluate results visually without additional equipment. These reagents allow in particular the differentiation of antibodies that are not clearly defined microscopically by indirect immunofluorescence. EUROASSAY and EUROLINE are also employed in laboratories where no sophisticated laboratory instruments are available.

EUROIMMUN produces an extensive range of Westernblot strip test systems and corresponding reagents for confirmation of positive fluorescence and ELISA results as well as clarification of difficult-to-interpret results in autoimmune diagnostics, infectious serology and allergology. Refined electrophoretical processes have been developed to allow the precise separation of diagnostically relevant proteins from one another. Lot-specific evaluation templates are produced for the evaluation of band patterns. The program ”EUROLineScan“ enables fully automated evaluation of membrane-based test systems and simplifies the archiving of results with large sample series.

One of the company’s main strengths is its technical expertise. This encompasses not just the manufacture and sale of medical laboratory diagnostics, but also the diagnostic application of the products in a reference laboratory which provides highly differential diagnostics. This reference laboratory has set standards in Germany, and worldwide is unequalled in the whole field of autoimmune diagnostics. The diagnostic spectrum of the laboratory also covers the areas of infectious serology and serological allergy diagnostics. The reference laboratory receives hundreds of serum samples daily from all over Germany as well as from many other countries. It helps EUROIMMUN customers to secure their results: a large proportion of serum samples sent to EUROIMMUN for evaluation are analysed free of charge in order to maintain high standards in the laboratories of EUROIMMUN customers. Customers can obtain further technical information from experienced scientists in the company, with whom they can also discuss serological problem cases. The “Institute for Quality Assurance”, an institution newly founded by EUROIMMUN, organises unbiased quality assessments and provides advice in the area of quality management. Moreover EUROIMMUN has established the “Institute for experimental Immunology”, which is engaged in basic research.

In October 2009, the EUROIMMUN workforce included 134 university and college graduates, among these biologists, biochemists, chemists, engineers and medical doctors (40 of them holding a doctor’s degree). Medical technicians are particularly strongly represented with 116 people, corresponding to EUROIMMUN’s activities, as well as biology/chemistry laboratory technicians (55). At present the company is training 51 young people as biology laboratory assistants, industrial clerks, IT specialists, electronic system technicians, electronic technicians for devices and systems, industrial mechanics, lathe operators and cooks as well as business information technology specialists and business economists (dual system). At EUROIMMUN great value is placed on advising customers and prospective customers in a factual, technical and commercially restrained manner and fully supporting them in the use of our diagnostically demanding products. EUROIMMUN products are backed by an energetic and competent sales force, qualified information material, didactic test instructions and scientifically based, but nevertheless understandable advertisements in technical journals. Advertising material is produced in-house using the latest desktop publishing methods, right up until the fully digitalised ready-for-exposure documents. The most important publications and posters are translated into many languages. EUROIMMUN has set up an informative homepage on the internet (www.euroimmun.com) which is visited extensively internationally.

Over 3,000 laboratories worldwide use EUROIMMUN diagnostics. 400 of these are in Germany. The company’s development is shaped by continuous growth. Although the diagnostic market in Germany stagnated and has become particularly strongly competitive, EUROIMMUN has been able to continue its strong expansion. The company is achieving an ever increasing independence from the German market, since more and more products are sold abroad. With their quality and standardization, EUROIMMUN products are capturing the leading position in the world.

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TECHNIQUES FOR THE SEROLOGICAL INVESTIGATION OF ANTIBODIES

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Techniques for the Serological Indirect Immunofluorescence: An Easy and Modern Method Investigation of Antibodies

Principle of the Test cell with antigen • For the determination of autoantibodies or antibodies against infectious agents, cells, tissue sections or purified, biochemically characterized substances are used as antigen substrates.

specific human • If the sample is positive, specific antibodies in the diluted serum sample attach antibody to the antigens coupled to a solid phase. • In a second step, the attached antibodies are stained with fluorescein-labelled anti-human antibodies and visualized with the fluorescence microscope. • Positive samples can be titrated in steps. The most suitable titration interval is provided by the dilution factor 3.162 (square root of 10). In this way, every second step represents in its denominator an integral power of 10 (1 : 10, 1 : 32, 1 : 100, 1 : 320, 1 : 1000, 1 : 3200, 1 : 10000 etc.). FITC

FITC-labelled anti- human antibody FITC

Indirect Immunofluorescence: A Standardized Technique for the Determination of Autoantibodies and Antibodies against Infectious Agents • High specificity: positive and negative samples produce a large difference in signal strength. Each bound antibody shows a typical fluorescence pattern depending on the location of the individual antigens. • The entire antigen spectrum of the original subtrate is available, thus allowing Pattern homog. Anti- Pattern fine-granular. the detection of a large number of antibodies and achieving a higher detection dsDNA? Anti-Histones? Anti-SS-A? Anti-SS-B? rate. • Immunofluorescence enables simultaneous detection of antibodies against several biochemically different antigens on one single biological substrate. • The indirect immunofluorescence test is the analytical method of choice when it would be too difficult or too complicated to prepare the test antigens indi- vidually for enzyme immunoassays.

Pattern nucleolar. Anti- Pattern cytoplasmic. PM-Scl? AMA M2? Differentiation of antibodies using HEp-2 cells.

tissue sections EUROIMMUN’s Innovations for the Standardization and Modern- antigen dots ization of Indirect Immunofluorescence culture cells • Activation technique: physically or chemically activated cover glasses are coated with cultured cells or tissue sections. Frozen tissue sections are fixed to the transf. cells glass surface by covalent bonding, increasing adhesion more than 100 times and thus preventing the substrates from being detached. • BIOCHIP Technology: cover glasses coated with biological substrates are cut into millimetre-sized fragments (BIOCHIPs) on a machine. This makes it possible to obtain ten or more first-class preparations of homogeneous quality per tissue section, in the case of cultured cell substrates even several thousands. • BIOCHIP Mosaics™: using several BIOCHIPs coated with different substrates side by side on one and the same reaction field, antibodies against various organs or infectious agents can be investigated simultaneously. Detailed antibody profiles can thus be established with comparatively little effort, allowing the reciprocal determination of the results on different substrates. • TITERPLANE™ Technique: samples or reagents are applied to the reaction fields of a reagent tray. The BIOCHIP Slides are then placed into the recesses of the reagent tray, where all BIOCHIPs come into contact with the fluids, and the individual reactions commence simultaneously. As the fluids are confined in a BIOCHIP Technology and Mosaics. closed space, there is no need for the use of a conventional „humidity chamber“.

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Indirect Immunofluorescence: An Easy and Modern Method

Chemically Activated Cover Glasses for Histochemistry

• For diagnostics of organ-specific or tissue-specific autoantibodies frozen tissue frozen tissue section frozen tissue section glutardialdehyde sections of various organs are used. However, formerly, the morphology of NH2 N Aminoethyl- HC O aminoproyl- (CH ) HC O HC tissues suffered during incubation in aqueous medium, tissue parts occasionally trimethoxysilane 2 3 (CH ) (CH ) HC O 2 3 2 3 NH2 became detached from slides, and the interpretation of results was difficult. HC HC (CH2)2 NH N N - 3 CH OH 2 - H O - H O • Using the activation technique for the first time in histology, we have applied NH 3 2 2 (CH2)2 (CH2)2 (CH2)2 Investigation of Antibodies (CH2)3

solid phase techniques. Firstly, the surface of cover glasses is coated with NH NH NH Techniques for the Serological H3CO Si OCH3

(CH2)3 (CH2)3 (CH2)3 spontaneously reactive aldehyde groups. In a second step, the tissue sections OCH3 Si O Si O Si O

are applied to the chemically activated cover glasses (Stöcker, W: European OH O O O Patent No. 0 117 262; U.S. Patent No. 4,647,543). Free amino groups of the tissue glass sections, especially of the hydroxylysine contained in the collagen, bind to the carrier material by covalent bonding. • This results in an increased adhesion of frozen tissue sections more than a hundredfold and prevents them from being detached during incubation. Fixation of frozen tissue sections to glass Furthermore, in some cases the activation technique results in a significantly surfaces by covalent bonding. better conservation of tissue structures, especially in organs which previously exhibited a generally low level of adhesion. Therefore, the tests can be evaluated with considerably greater confidence.

Determination of Low-Avidity Antibodies • An alternative principle for the serological diagnosis of fresh infections has been established by investigating the antibody avidity. • The first reaction of the immune system following an infection is the formation of low-avidity antibodies. As the infection proceeds, increasingly antigen-adapted IgG is formed, and avidity grows. As long as high-avidity IgG is not yet detected in the serum, it can be assumed that the infection is still in an early stage. • To identify low-avidity antibodies in a patient’s serum, two immunofluorescence tests are performed in parallel: one test is carried out in the conventional way, low-avide Ab against EBV-CA the other one includes urea treatment between incubations with patient’s serum and peroxidase-labelled anti-human IgG, resulting in the detachment of low- avidity antibodies from the antigens. • Low-avidity antibodies are present if the fluorescence intensity is significantly reduced (two intensity levels ore more) by urea treatment. • The following test kits for avidity determination are available: Toxoplasma gondii, Rubella virus, West-Nile virus, CMV, EBV-EA, EBV-CA.

high-avide Ab against EBV-CA without urea with urea

EUROPLUS™ System: Combination of conventional immuno- fluorescence substrates and monospecific tests • In EUROPLUS™ immunofluorescence tests antibody detection is performed using both tissue sections/cell substrates and monospecifically reacting antigens. • Antibodies detected in IFT screening tests can therefore be differentiated or confirmed with one and the same reaction field. In some cases, the antigens help to extend the antigen spectrum, offering a wider range for screening. • BIOCHIPs coated with purified or recombinant antigens are used as monospecific substrates. • In case of a positive result the antigens fluoresce green in defined areas under the microscope. • In some EUROPLUS™ test systems several different antigens are coated on one EUROPLUS™: BIOCHIP combination of tissue BIOCHIP in separate antigen rows. In this manner, several monospecific analyses sections / cell substrates (left) and purified can be performed using a single BIOCHIP. antigens (right). • Available EUROPLUS™ substrates: MPO, PR3, gliadin GAF-3X, OspC, VlsE, Plasmodium falciparum und vivax, gp125, p19.

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Techniques for the Serological Indirect Immunofluorescence: An Easy and Modern Method Investigation of Antibodies

New: Hydrophobic Slides • EUROIMMUN has developed a specific slide surface with hydrophobic properties. • This prevents the droplets from spreading on the slide surface. The slides are now suitable for manual incubation using TITERPLANE Technique and non- manual incubation on automated systems. • The reaction fields must not be marked with a Cytomation Pen anymore. • Price and order number are the same as for conventional EUROIMMUN slides (please add "hydrophobic" when ordering) • Hydrophobic slides are available on request for many products.

Above: conventional slide Below: hydrophobic slide.

AP16 IF Plus by DAS: Automated Solution for all EUROIMMUN Immunofluorescence Tests • Various validated parameters. Slide definitions and test files available. • CE conformity for device/test system combination. • Capacity: 16 slides, 80 samples, 200 dilutions. • Programmable for 8 methods per run. • 12 dilution series freely programmable. • Automated sample dilution, sample and reagent dispension, incubation and washing of slides. • Laboratory software interface. • The incubation protocol for result documentation is automatically created from AP16 IF Plus by DAS. the worklist. • Barcode reader available on request.

Fluorescence Microscope EUROStar II • The EUROStar II is specifically tailored to the requirements of indirect immuno- fluorescence. Unnecessary and partly expensive components have been de- liberately left out of the design and the conventional complex illumination fittings have been replaced by the stunningly simple EUROStar Bluelight system. • With the EUROStar Bluelight, engineers at EUROIMMUN AG have introduced blue light-emitting diodes to fluorescence microscopy. Almost all the emitted light is suitable for the excitation of fluorescein. • The EUROStar Bluelight does not emit any ultraviolet radiation and is explosion proof. • The EUROStar Bluelight is immediately ready for operation after being switched off and offers instant full output after being switched on again. The LED shines for 50,000 hours – which is 500 times longer than a mercury vapour lamp. Thus, the microscope requires almost no maintenance. • With its halogen transmitted-light source, the version EUROStar II Plus is suited for brightfield, darkfield, phase contrast or polarisation microscopy. • EUROStar was designed to accommodate the additional assembly of a digital camera.

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BIOCHIP Mosaics™ Investigation of Antibodies Techniques for the Serological

Slides for indirect immunofluorescence can be produced with single substrates or BIOCHIP Mosaics™ from up to 45 different substrates according to your individual requirements. thyroid gland, parathyroid gland, pancreas, adrenal gland, ovary, placenta*, testis, spermatozoa, pituitary gland, hypothalamus*, cerebrum, cerebellum, brain stem, pons*, lobus temporalis, substantia nigra*, peripheral nerve, spinal cord, optic nerve (AQP-4, NMO IgG) eye, granulocytes (fixed with EOH, HCHO or MOH), lactoferrin-specific granulocytes, lymphocytes, monocytes*, thrombocytes, kidney (primate, rat, mouse), lung*, liver (primate, rat, mouse), mouth mucosa, stomach (corpus, antrum), jejunum, colon, intestinal goblet cells, umbilical cord, mamma, lacrimal gland, parotid gland, prostate, vesicula seminalis, skeletal muscle, F-actin (VSM47), heart muscle, thymus, lipocytes, cartilage*, epidermis, oesophagus (primate, rat), tongue, lip, melanocytes, HEp-2 cells, HEp-20-10 cells, HUVEC, Crithidia luciliae sensitive etc. Adenovirus, Afipia felis*, Bartonella henselae, B. quintana, Bordetella parapertussis, B. pertussis, Borrelia afzelii, B. burgdorferi sensu stricto (strains CH, USA), B. garinii, Campylobacter coli*, C. jejuni, Candida albicans, C. glabrata*, C. krusei*, C. parapsilosis*, C. tropicalis*, Chikungunya virus, Chlamydia pneumoniae, C. trachomatis, C. psittaci, CMV, Coxsackievirus (A7, A9, A16, A24, B1 to B6), Crimean Congo fever virus, Dengue virus type 1 to 4, EBV-CA, EBNA, EBV- EA, Echinococcus granulosus, ECHO virus, Hantavirus, Haemophilus influenzae*, Helicobacter pylori, HHV-6, HSV-1, HSV-2, Influenza virus A (strains H3N2, H1N1, H5N1), Influenza virus B, Japanese encephalitis virus, Klebsiella pneumoniae*, Legionella bozemanii*, L. dumoffii*, L. gormanii*, L. jordanis*, L. longbeachae, L. micdadei*, L. pneumophila (serotypes 1 to 14), Leishmania donovani, Listeria monocytogenes (1/2a and 4b)*, measles virus, mumps virus, Mycoplasma hominis, M. pneumoniae, Parainfluenza virus type 1 to 4, Rift valley fever virus*, RSV, rubella virus, Saccharomyces cerevisiae, SARS-CoV, TBE virus, TO.R.C.H. profile, Toxoplasma gondii, Treponema pallidum, T. phagedaenis, Ureaplasma urealyticum, VZV, West Nile virus, Yellow fever virus, Yersinia enterocolitica (O:3, O:4, O:6 and O:9)*. EUROPLUS™: HEp-2/liver + RNP/Sm, Sm, SS-A, SS-B, Scl-70, rib. P-proteins, Jo-1; granulocytes + MPO, PR3; primate stomach (parietal cells) + intrinsic factor; primate liver (endomysium) + gliadin (GAF-3X); rat kidney + AMA M2; thyroid gland + thyroglobulin; Borrelia burgdorferi and afzelii + OspC and VlsE, Plasmodium falciparum (HRP-2, MSP-2), P. vivax (MSP, CSP). Transfected cells: rPAg 1 + 2 (pancreas antigen 1 + 2), AQP-4, glutamate receptor (type NMDA), desmoglein 1 + 3, BP230. * Currently not available in the European Union.

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Techniques for the Serological The Indirect Immunofluorescence Test, Performed Using the Investigation of Antibodies TITERPLANE™ Technique

(Reaction fields 5 x 5 mm)

The TITERPLANE™ Technique was developed by EUROIMMUN in order to standardize immunological analyses: Samples or labelled antibodies are applied to the reaction fields of a reagent tray. The BIOCHIP Slides are then placed into the recesses of the reagent tray, where all BIOCHIPs of the slide come into contact with the fluids, and the individual reactions commence simultaneously. Position and height of the droplets are exactly defined by the geometry of the system. As the fluids are confined in a closed space, there is no need for the use of a conventional ”humidity chamber”. It is possible to incubate any number of samples next to each other and simultaneously under identical conditions. Prepare: Check the reagent tray: Are the reaction fields hydrophiIic and the surrounding coating hydrophobic? If not, rub with a wet paper towel, using normal household detergent or Extran MA 01 (Merck) if necessary, and rinse thoroughly with water. For occasional disinfection, immerse for 1 h in 3% Sekusept Extra (Henkel) in water. Open the individual packets containing the BIOCHIP Slides only after they have reached room temperature. Do not touch the BIOCHIPs. Mark BIOCHIP Slides as required with a felt pen. Dilute: Dilute serum samples according to the user’s test protocol. Include positive and negative controls with every test procedure. Mix control sera before use. Pipette: Apply 25 µl of diluted serum to each reaction field of the reagent tray, avoiding air bubbles. Transfer all samples to be tested before starting the incubation (up to 200 droplets). Use a polystyrene pipetting template. Incubate: Start reactions by fitting the BIOCHIP Slides into the corresponding recesses of the reagent tray. Ensure that each sample makes contact with its BIOCHIP and that the individual samples do not come into contact with each other. Incubate for 30 min at room temperature. Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker, and immerse them immediately afterwards in a cuvette containing PBS-Tween for at least 5 min. Pipette: Apply 20 µl of fluorescein-labelled anti–human immunoglobulin (conjugate) onto each reaction field of a clean reagent tray. Add all drops (reagent for a maximum of 50 slides) before continuing incubation. Use a stepper pipette. The labelled anti-human serum should be mixed with a pipette before use. To save time, conjugate can be pipetted onto separate reagent trays during incubation with the diluted serum. Incubate: Remove one BIOCHIP Slide from the PBS-Tween and within five seconds blot only the back and the long edges with a paper towel and immediately put the BIOCHIP Slide into the recesses of the reagent tray. Do not dry the areas between the reaction fields. Check for correct contact between the BIOCHIPs and liquids. Then continue with the next BIOCHIP Slide. From now on, protect the slides from direct sunlight. Incubate for 30 min at room temperature. Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker and put them in a cuvette containing PBS-Tween for at least 5 min. 10 drops of Evans Blue (150 µl) for each 150 ml phosphate buffer can be added for counterstaining. Embed: Place glycerol/PBS onto a cover glass – drops of 10 µl per reaction field. Use a polystyrene embedding template. Remove one BIOCHIP Slide from the PBS-Tween and dry the back and all four edges as well as the surface around, but not between, the reaction fields with a paper towel. Put the BIOCHIP Slide, with the BIOCHIPs facing downwards, onto the prepared cover glass. Check immediately that the cover glass is properly fitted into the recesses of the slide. Correct the position if necessary. Now proceed in the same way with the next BIOCHIP Slide. Evaluate: Read the fluorescence under the microscope.

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The Indirect Immunofluorescence Test, Performed Using the TITERPLANE™ Technique

slide

BIOCHIPs reagent tray Investigation of Antibodies Techniques for the Serological Pipette: 10 µl per field (3 x 3 mm) 25 µl per field (5 x 5 mm) diluted samples 70 µl per field (7 x 9 mm)

Incubate: 30 min

Wash: 1 s flush PBS- 5 min cuvette Tween

Pipette: 10 µl per field (3 x 3 mm) 20 µl per field (5 x 5 mm) labelled antibody

60 µl per field (7 x 9 mm)

Incubate: 30 min

Wash: 1 s flush PBS- 5 min cuvette Tween

Embed: 10 µl per field (3 x 3 mm) glycerol/PBS 10 µl per field (5 x 5 mm) 20 µl per field (7 x 9 mm) cover glass

20x Evaluate: fluorescence microscopy NEOFLUAR

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Techniques for the Serological Recommended Serum Dilutions for Indirect Immunofluorescence Investigation of Antibodies – Autoimmunity –

Antibodies against Substrate IgA IgG IgM IgAGM

acetylcholine receptor *skeletal muscle, monkey / heart, monkey 100 actin Hepatitis Mosaic** 10 10 100 ADH-producing cells nucl. supraopticus & paraventricularis, monkey 10 10 adrenal cortex adrenal gland, monkey 10 alveolar basement membrane lung, monkey / kidney, monkey 10

aquaporin-4 Neurology Mosaic 10 asialoglycoprotein receptors *Hepatitis Mosaic** 100 basic myelin protein (BMP) cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 bile canaliculi Hepatitis Mosaic** 100 100 bile duct epithelium Hepatitis Mosaic** 10 + 100

BP180 Dermatology Mosaic (EUROPLUS) 10 BP230 Dermatology Mosaic (transfected cells) 10 brain: grey matter cerebellum, monkey / intestinal tissue, fetal monkey 10 + 100 10 brain: white matter cerebellum, monkey / intestinal tissue, fetal monkey 10 + 100 10 cANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 1

cartilage trachea, fetal monkey 10 10 cell nuclei (ANA) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 CENP-F *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 centromere HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 cerebrum gyrus precentralis, monkey 10 + 100 10

chondroitin sulfate trachea / cartilage, monkey 10 10 10 collagen type VII oesophagus, monkey or tongue, monkey 10 10 collagenous connective tissue pancreas, monkey 10 10 colon (epithelial cells) intestinal tissue, fetal monkey 10 10 cornea eye, monkey 10 10

cyclin I (PCNA) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 cyclin II (mitosin) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 cytoskeleton HEp-2 cells / liver, monkey 100 100 + 1000 + 10000 100 desmoglein 1+3 transfected cells 10 desmosomes oesophagus, monkey or tongue, monkey 10

dsDNA *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 dsDNA Crithidia luciliae 10 10 elastin stomach, rat / kidney, rat 10 endocardium endocardium, monkey / intestinal tissue, fetal monkey 10 endomysium liver, monkey 10 10

endoplasmatic reticulum HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 endothelial cells lung, monkey 10 10 endplates *skeletal muscle, monkey / heart, monkey 100 enterocytes intestinal tissue, fetal monkey 10 10 eosinophilic granulocytes granulocytes (EOH) / liver, monkey 10 10 + 100 1

epidermal basement membrane oesophagus, monkey or tongue, monkey 10 10 eye muscle eye, monkey 10 fibrillarin (U3-nRNP) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 filaggrin oesophagus, rat 10 10 ganglion cells ganglion stellatum, monkey / intestinal tissue, fetal monkey 10 10

gastric mucosa stomach, monkey 10 gastrin-producing cells stomach (antrum), monkey / stomach (corpus), monkey 10 10 glandula suprarenalis adrenal gland, monkey 10 gliadin *intestinal tissue, fetal monkey / gliadin dots 10 10 glomerular basement membrane (GBM) kidney, monkey 10 10

glutamate receptor type NMDA transfected cells 10 glutamic acid decarboxylase (GAD) cerebellum, monkey / pancreas, monkey 10 + 100 10 goblet cells goblet cells (culture) 10 10 Golgi apparatus HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 hair follicle epidermis, monkey 10 10

*) In addition to the preferential analysis or as a plausibility check. **) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat.

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Recommended Serum Dilutions for Indirect Immunofluorescence – Autoimmunity –

Antibodies against Substrate IgA IgG IgM IgAGM

heart muscle skeletal muscle, monkey / heart, monkey 100 100 heart valves mitral valve, monkey 10 10 histones *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 Hu cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 Investigation of Antibodies Techniques for the Serological hypothalamus nucl. supraopticus & paraventricularis, monkey 10 10 inner ear inner ear, rat or guinea pig 10 10 intercalated discs heart, monkey 100 100 intestinal epithelial tissue intestinal tissue, fetal monkey 10 10 intrinsic factor *stomach, monkey / intrinsic factor 10 10 Jo-1 *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

keratin oesophagus, monkey or tongue, monkey 10 10 keratin, RA-associated (filaggrin) oesophagus, rat 10 10 Ku *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 labyrinth inner ear, rat or guinea pig 10 10 lacrimal gland (excretory ducts and acini) lacrimal gland, monkey 10 10

laminin epidermis, monkey / lung, monkey / kidney, monkey 10 10 lamins HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 lipocytes fat tissue, monkey 10 10 liver membrane (LMA) Hepatitis Mosaic** 100 liver-kidney microsomes (LKM) Hepatitis Mosaic** 100

liver-pancreas antigen (LP) Hepatitis Mosaic** / pancreas, monkey 100 liver-specific protein (LSP) Hepatitis Mosaic** 100 lymphocytes Lymphocytes 10 + 100 10 + 100 lysosomes HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 M2 *Hepatitis Mosaic** 100 + 1000 + 10000 100

M3 *Hepatitis Mosaic** 100 + 1000 + 10000 100 M4 *Hepatitis Mosaic** 100 + 1000 + 10000 100 M5 *Hepatitis Mosaic** 100 + 1000 + 10000 100 M6 *Hepatitis Mosaic** 100 + 1000 + 10000 100 M7 *Hepatitis Mosaic** 100 + 1000 + 10000 100

M8 *Hepatitis Mosaic** 100 + 1000 + 10000 100 M9 *Hepatitis Mosaic** 100 + 1000 + 10000 100 medullated nerves cerebellum, monkey / nerves, monkey 10 + 100 melanocytes retina, monkey 10 10 Mi-1 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

Mi-2 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 mitochondria (AMA) kidney, rat / stomach, rat / M2 dots / HEp-2 cells 100 + 1000 + 10000 100 mouth mucosa mouth mucosa 10 10 10 myelin cerebellum, monkey / nerves, monkey 10 + 100 myelin-associated glycoprotein (MAG) cerebellum, monkey / nerves, monkey 10 + 100

myeloperoxidase (MPO) granulocytes (EOH), human / liver, monkey 10 10 + 100 1 myocardium skeletal muscle, monkey / heart, monkey 100 100 myolemma skeletal muscle, monkey / heart, monkey 10 + 100 10 + 100 myosin skeletal muscle, monkey / heart, monkey 100 100 native collagen pancreas, monkey 10

nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 neuroendothelium cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 neurofilaments cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 NOR HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 nRNP HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

ovary ovary, monkey 10 10 pANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 1 pancreas acini (Crohn’s disease autoantigen) pancreas, monkey 10 10 pancreas islets pancreas, monkey (1st step: 18 hours) 10 10 pancreas, excretory duct epithelium pancreas, monkey 10 10 10

*) In addition to the preferential analysis or as a plausibility check. **) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat.

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Produktkatalog2010.p65 13 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological Recommended Serum Dilutions for Indirect Immunofluorescence Investigation of Antibodies – Autoimmunity –

Antibodies against Substrate IgA IgG IgM IgAGM

parathyroid gland parathyroid gland, monkey 10 10 parietal cells stomach (corpus), monkey 10 10 10 + 100 parotid gland parotid gland, monkey 10 10 peripheral nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 pituitary gland, anterior lobe pituitary gland, monkey 10 10 placenta placenta, human 10 PM-1 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 proinsulin *pancreas, monkey 10 10 prostate prostate, monkey 10 proteinase 3 (PR3) granulocytes (EOH), human / liver, monkey 10 10 + 100 1

Purkinje cell cytoplasm (Yo) cerebellum, monkey 10 + 100 10 + 100 RANA Raji cells / HEp-2 cells 10 10 reticulin intestinal tissue, fetal monkey 10 10 10 reticulocytes bone marrow, monkey 10 10 retina retina, monkey 10 10

Ri cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 ribosomal P-proteins HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 ribosomes HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 RNA polymerase HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 RNA HEp-2 cells / liver, monkey 100 + 1000 + 10000 100

salivary glands (acini and excretory ducts) parotid gland, monkey 10 10 sarcolemma skeletal muscle, monkey / heart, monkey 10 + 100 10 + 100 Scl-70 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 signal recognition particle (SRP) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 skeletal muscle skeletal muscle, monkey / heart, monkey 100 100

Sm HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 smooth muscles (ASMA) stomach, rat / kidney, rat 100 100 spermatozoa spermatozoa smear, human 10 10 10 spindle fibers HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 spleen spleen, monkey 10 + 100

SS-A (Ro) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 SS-B (La) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 ssDNA *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 striated muscles skeletal muscle, monkey / heart, monkey 100 100 substantia nigra substantia nigra, monkey 10 10 + 100

synovialis joint cartilage, monkey 10 10 testis testis, monkey 10 10 thrombocytes (bound antibodies) thrombocyte smear – – – thrombocytes (free antibodies) thrombocytes, human 10 10 10 thymus thymus, monkey 10 10

thyroglobulin thyroid gland, monkey or struma, human/TG 10 + 100 10 thyroid colloid type II thyroid gland, monkey or struma, human 10 10 thyroid microsomes thyroid gland, monkey or struma, human 10 + 100 10 trachea trachea, monkey 10 10 tubular basement membrane kidney, monkey 10 10

U1-nRNP *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 vasopressin-producing cells nucl. supraopticus & paraventricularis, monkey 10 10 vestibular organ inner ear, rat or guinea pig 10 10 vimentin *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 ”xANCA” granulocytes (EOH, acetone, HCHO) / liver, monkey 10 10 + 100 1

*) In addition to the preferential analysis or as a plausibility check.

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Produktkatalog2010.p65 14 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Recommended Serum Dilutions for Indirect Immunofluorescence – Infectious Serology –

Antibodies against IgA IgG IgM

Adenovirus (type 3) 10 + 100 10 + 100 10 Afipia felis 100 100 + 1000 10 Bartonella henselae 100 + 320 + 1000 100 Bartonella quintana 100 + 320 + 1000 100

Bordetella parapertussis 10 + 100 100 + 1000 100 + 1000 Investigation of Antibodies Techniques for the Serological Bordetella pertussis 10 + 100 100 + 1000 100 + 1000 Borrelia afzelii 100 + 320 + 1000 10 Borrelia burgdorferi sensu stricto (strains CH and USA) 100 + 320 + 1000 10 Borrelia garinii 100 + 320 + 1000 10 Borrelia OspC 10

Borrelia VlsE 100 Campylobacter coli 100 100 + 1000 10 Campylobacter jejuni 320 1000 100 Candida albicans 100 + 1000 1000 + 10000 100 Candida glabrata 100 + 1000 1000 + 10000 100

Candida krusei 100 + 1000 1000 + 10000 100 Candida parapsilosis 100 + 1000 1000 + 10000 100 Candida tropicalis 100 + 1000 1000 + 10000 100 Chikungunya virus 10 + 100 10 + 100 Chlamydia pneumoniae (IFA) 100 100 + 1000 10

Chlamydia pneumoniae (MIF) 10 100 10 Chlamydia trachomatis (IFA) 100 100 + 320 + 1000 10 Chlamydia trachomatis (MIF) 10 100 10 Chlamydia psittaci (MIF) 10 100 10 CMV 100 100 + 1000 100

Coxsackie virus types A7, A9, A16, A24, B1 to B6 10 + 100 100 + 1000 10 Dengue virus 10 100 + 1000 10 + 100 EBV-CA, -EA 10 + 100 10 + 100 + 1000 10 + 100 EBNA 10 + 100 Echinococcus granulosus 100 100 + 320 + 1000 100

Echo virus (type 7, 19) 10 + 100 100 + 1000 10 Hanta virus 100 + 1000 100 + 1000 100 + 1000 Haemophilus influenzae 100 1000 + 10000 10 Helicobacter pylori 100 100 + 1000 10 HIV-1/2 10 + 100

HHV-6 10 + 100 10 HSV-1/2 10 100 + 1000 + 10000 10 Influenza virus type A 10 10 + 100 10 Influenza virus type B 10 10 + 100 10 Klebsiella pneumoniae 100 100 100

Legionella pneumophila (all serotypes) 100 + 320 + 1000 Leishmania 100 320 100 Listeria monocytogenes (type 1/2a, 4b) 100 100 + 1000 100 measles virus 10 10 + 100 10 mumps virus 10 10 + 100 10

Mycoplasma hominis 10 10 + 100 10 Mycoplasma pneumoniae 10 10 + 100 10 Parainfluenza virus types 1 - 4 10 + 100 10 + 100 + 1000 10 Plasmodium falciparum/vivax 32 + 100

rubella virus 10 + 100 10 + 100 10 + 100 RSV 10 10 + 100 + 1000 10 Saccharomyces cerevisiae 100 1000 100 TBE virus 10 10 + 100 + 1000 10 + 100 Toxoplasma gondii 16+64+256 16+64+256+1028... 16+64+256

Treponema pallidum 10 10 + 100 10 Ureaplasma urealyticum 10 10 + 100 10 VZV 10 10 + 100 10 West-Nile virus 10 + 100 + 1000 10 + 100 Yersinia enterocolitica O:3; O:4; O:6; O:9 10 + 100 100 10 + 100

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Produktkatalog2010.p65 15 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Diagnostically Relevant Autoantibodies

Techniques for the Serological Systemic Autoantibodies against Investigation of Antibodies Ig- AGM A G M BASIS SPECTRUM Ig- AGM A G M SYSTEMIC LUPUS Ig- AGM A G M POLYMYOSITIS, DERMATOMYOSITIS 151 ANA (cell nuclei) IF global testing ERYTHEMATOSUS (SLE) 151 ANA (cell nuclei) IF global testing 152 ANA profile differentiation 151 ANA (cell nuclei) IF global testing 1530 Myositis Profile 3 EUROLINE 1572 dsDNA-NcX ELISA 1574 nucleosomes SLE specific (Mi-2, Ku, PM-Scl100, PM-Scl75, SRP, Jo-1, 1572 dsDNA IFT SLE specific 1572 dsDNA ELISA PL-7, PL-12, OJ, EJ, Ro-52) 1590 ENA ProfilePlus ELISA 1 1572 dsDNA IFT (C. luciliae) SLE specific 1661 Jo-1 nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1 1572 dsDNA RIA 1662 PL-7 1590 ENA ProfilePlus ELISA 2 159 ENA PoolPlus ELISA 1663 PL-12 rib. P proteins, RNP/Sm, Sm, SS-A, 1591 U1-nRNP 1664 OJ SS-B, Scl-70, Jo-1, CENP B 1593 Sm SLE specific 1665 EJ 1590 SLE Profile ELISA (dsDNA, histones, rib. 1595 SS-A (Ro) 1666 SC P prot., nRNP/Sm, Sm, SS-A, SS-B, Scl-70) 159s SS-A 52 kDa: recombinant 1667 KS 162 AMA (mitochondria) 159t SS-A 60 kDa: recombinant 1584 PM-Scl (PM-1) 171 ASMA (smooth muscle) 1597 SS-B (La) 1616 SRP (signal recognition particle) 120 cANCA* (granulocytes) Wegener’s dis. 1640 ribosomal P proteins SLE specific 159s SS-A 52 kDa: recombinant 121 pANCA* (granulocytes) vasculitis 1605 Ku 1605 Ku 1010 autoantibody profile 10 IF substrates 1601 cyclin I (PCNA) 1607 Mi-2 1030 autoantibody profile 30 IF substrates 156 histones (global testing) 1635 serotonin ab 1576 ssDNA (single-stranded DNA) 1636 PMR (polymyalgia rheumatica factor) Ig- AGM A G M ANA DIAGNOSTICS, WESTERNBLOT 121 pANCA* (granulocytes) vasculitis 1520 PM-Scl, CENP A/B, Ku 86 and 72 kDa, Ig- AGM A G M (RHEUMATOID) ARTHRITIS M2 74 kDa, RNP 70 kDa, RNP A/C, Ig- AGM A G M SJÖGREN’S SYNDROME 1505 CCP (cyclic citrullinated peptides) Sm B/B’/D, SS-A 60 and 52 kDa, 151 ANA (cell nuclei) IF global testing 151a Sa SS-B 52, 47, 44 and 43 kDa, ribosomal 1595 SS-A (Ro) 1814 RF IgM (class. rheumatoid factor) P proteins P0/P1/P2, Scl-70, Jo-1) 159s SS-A 52 kDa: recombinant 1508 filaggrin (RA keratin) 159t SS-A 60 kDa: recombinant 1219 GS ANA (granulocyte specific ANA) Ig- AGM A G M OTHER AUTOANTIBODIES 1597 SS-B (La) 151 ANA (cell nuclei) IF global testing 1612 centrioles 1604 RANA (rheum. arthritis nuclear antigen) 1613 MSA-1 (NuMa, spindle fibres) Ig- AGM A G M ANTI-PHOSPHOLIPID 121 pANCA* (granuloc.) RF-ass. vasculitis 1614 MSA-2 (midbody) SYNDROME (APS) 148 cartilaginous subst. polychondritis 1615 MSA-3 (chromosome-ass. antigen) 1621 cardiolipin 194 collagen (global testing) 1617 centromer F protein (CENP-F) 1632 ß-2-glycoprotein 1 1947 collagen type VII 1641 ribosomes 1631 lupus anticoagulant (plasma)** 1642 Golgi apparatus 162a phosphatidylserine FURTHER RHEUMATOID RELEVANT 1643 lysosomes Ig- AGM A G M ANALYSES 165 cytoskeleton Ig- AGM A G M PROGRESSIVE SYSTEMIC SCLEROSIS 2011 anti-streptolysin 1651 actin 151 ANA (cell nuclei) IF global testing 2012 anti-streptokinase 1652 vimentin 1599 Scl-70 (DNA topoisomerase I) 2013 anti-streptodornase 1653 cytokeratin 1584 PM-Scl (PM-1) 2014 anti-DPNase (anti-NADase) 1654 tropomyosin 1611 centromeres 2031 anti-staphylolysin 1655 vinculin 1611 centromere B protein (recombinant) 2034 anti-hyaluronidase 1656 desmin 1582 U3-nRNP (fibrillarin) 213 Borrelia burgdorferi 1659 laminin (basal membranes) 1583 RNA polymerase I, II, III 2171 Yersinia enterocolitica O:3 194 collagen (global testing) 1585 7-2-RNP (To) 2191 Chlamydia trachomatis 1947 collagen type VII 1586 4-6-S-RNA 1950 elastin 1587 NOR (nucleolus organizer region) IMMUNOGLOBULINS: 196 vessel endothelium Ig- AGM A G M ANTI- Ig- AGM A G M SHARP’S SYNDROME MCTD 1811 human IgA Ig- AGM A G M THERAPY CONTROL 1591 U1-nRNP 1813 human IgE 1821 interferon alpha*** 151 ANA (cell nuclei) IF global testing 1814 human IgG 1822 interferon beta 1815 human IgM 1824 erythropoetin Ig- AGM A G M CREST SYNDROME 1572 dsDNA RIA 1611 centromeres CIRC. IMMUNE COMPLEXES 1818 CIC-C1q ELISA 1611 centromere B protein (recombinant) 1818 C1q ELISA

Grey boxes: standard analysis *) ANCA diagnostics in acute cases within one hour, at any hour **) Use special procedure for taking sample(s) ***) Send frozen sample(s)

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Produktkatalog2010.p65 16 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Diagnostically Relevant Autoantibodies

Organ-/Tissue-Specifi c Autoimmunity: Autoantibodies against Ig- AGM A G M AUTOANTIBODY PROFILE Ig- AGM A G M WEGENER’S DISEASE, VASKULITIS* Ig- AGM A G M LIVER, BILIARY DUCTS 1030 30 IF substrates (BIOCHIPs) 120 cANCA IFT* granuloc. Wegener’s dis. 130 Liver Ab IFT global testing, 6 BIOCHIPs 1201 PR3 (proteinase 3) 130 Autoimmune Liver Dis. Ab Profile Ig- AGM A G M THYROID GLAND 1202 BPI (CAP 57) EUROLINE AMA-M2, 3E (BPO), Sp100, 1015 TRAb (TSH receptors) 121 pANCA IFT* granulocytes vasculitis PML, gp210, LC-1, LKM-1, SLA/LP, Ro-52 1012 TPO ab (thyroidea peroxidase) 1211 MPO (myeloperoxidase) 1013 TAb (thyroglobulin) 1212 elastase Autoimmune hepatitis (AIH) 1014 colloid antigen II ab 1213 cathepsin G 1302 SLA/LP (soluble liver antigen) 1011 MAb (microsomes) 1215 lactoferrin 1651 F-actin 1016 T3 ab 120 ANCA Profile ELISA 151 ANA (cell nuclei) IF global testing 1017 T4 ab PR3, MPO, elastase, cath. G, BPI, lactoferrin 1307 LC-1 (liver cytosol) 151 ANA (cell nuclei) IF global testing 132 LKM (liver kidney microsomes) Investigation of Antibodies Ig- AGM A G M DIABETES MELLITUS 195 elastin 1321 LKM-1 ELISA Techniques for the Serological 1021 ICA (islet cell antibodies) 196 vessel endothelium 1322 LKM-2 1022 GAD (glutamic acid decarboxylase) 1323 LKM-3 1023 IA-2 (tyrosine phosphatase) Ig- AGM A G M KIDNEY, LUNG 1303 ASGPR (asialoglycoprotein receptors) 1024 insulin ab human 120 cANCA IFT* granuloc. Wegener’s dis. 171 ASMA (smooth muscles) 1025 insulin receptor 121 pANCA IFT* granulocytes vasculitis 1301 LSP (liver-specific protein) 1026 glucagon-producing cells 125 kidney IF global testing 1304 LMA (liver cell membrane) 147 lipocytes 1251 GBM ELISA glomerular basal membrane 151 ANA (cell nuclei) IF global testing Primary biliary cirrhosis (PBC) 1572 dsDNA IFT 162 AMA (mitochondria) Ig- AGM A G M (POLY-)ENDOCRINOPATHY 1252 TBM (tubular basal membrane) 1622 AMA-M2 (PDH + BPO) 1051 adrenal cortex Addison’s dis. 1271 lung alveolar basal membrane 1624 AMA-M4 (sulfitoxidase) 1053 21-hydroxylase Addison’s dis. 1629 AMA-M9 (glycogen phosphorylase) 1061 ovary: theca cells Ig- AGM A G M NERVOUS SYSTEM 1603 Sp100 (nuclear dots) 1062 ovary: corpus luteum 111 Neuronal Ab IFT global testing 1608 GP210 (nuclear membrane, lamin) 1081 testis: Leydig cells 105 steroid hormon-producing cells Paraneoplastic neurol. syndromes Primary-sclerosing cholangitis (PSC) 104 parathyroid gland 1111 Neuronal Antigens Profile 2 121 pANCA (granulocytes) 1021 ICA (islet cell antibodies) EUROLINE amphiphysin, CV2.1***, 1012 TPO ab (thyroidea peroxidase) PNMA2 (Ma-2), Ri, Yo, Hu further antibodies 1361 H+/K+-ATPase ab ELISA 1112 Tr (Purkinje cell cytoplasm) 1305 bile ducts 1361 PCA (parietal cells) 1113 Yo (Purkinje cell cytoplasm; PCA-1) 1306 bile canaliculi 1091 pituitary gland: anterior lobe 1114 PCA-2 (Purkinje cell cytoplasm) 1609 coilin; P80 (few nuclear dots) 1092 pituitary gland: posterior lobe 1115 Ri (neurone nuclei; ANNA-2) 1011 MAb (thyroid microsomes) 1116 Hu (neurone nuclei; ANNA-1) Ig- AGM A G M STOMACH, INTESTINE 1052 adrenal medulla 112d NMDA receptors 1361 PCA (parietal cells) atroph. gastritis 107 placenta 1117 Ma1/Ma2 (neurone nuclei; Ta) 1361 H+/K+-ATPase ab atroph. gastritis 110 VPZ (vasopr.-prod. cells) D. insipudus 1119 CV2 (oligodendrocytes) 1362 intrinsic factor ab vit. B12 deficiency 1022 GAD stiff-person syndr. 1366 gastrin (G) cells Ig- AGM A G M INFERTILITY 112e amphiphysin stiff-person syndr. 1391 pancreas acinus cells Crohn’s dis. 1621 cardiolipin 112a AGNA (anti-glia nuclear antigen; SOX-1) 1391 CUZD1 Crohn’s dis. 1060 ovary: theca c., c. luteum, z. pellucida 112b ANNA-3 1392 GP2 Crohn’s dis. 1081 testis: Leydig cells 112c CRMP-5 (oligodendrocytes) 2841 Saccharomyces cerev. Crohn’s dis. 1086 spermatozoa 1392 pankreas secretion Crohn’s dis. 1091 pituitary gland: anterior lobe further parameters 135 mouth mucosa Behçet’s/ Crohn’s dis. 107 placenta 1154 aquaporin-4 neuromyelitis optica 1381 intestinal goblet cells ulc. colitis 1401 prostate 1153 NMO-IgG neuromyelitis optica 121 pANCA (granulocytes) ulc. colitis 1156 MOG (myelin-oligodendroc. glykoprot.) 1382 enterocytes Crohn’s dis. , ulc. colitis Ig- AGM A G M EPIDERMIS 1111 substantia nigra 191 endomysium GSE, Duhring’s dis. 1501 desmosomes pemphigus 1121 myelin 191 transglutaminase GSE, Duhring’s dis. 1495 desmoglein 1 pemphigus 1122 MBP (myelin-basic protein) 3011 deamidated gliadin (Z-AGFA) GSE 1496 desmoglein 3 pemphigus 1123 MAG (myelin-assoc. glycoprotein) 192 reticulin GSE, Duhring’s dis. 1502 epiderm. basal membr. pemphigoid 1124 myelin of peripheral nerves 1502 BP180 bullous pemphigoid 1126 neuroendothelium EXOCRINE GLANDS, PANCREATITIS, 1502 BP230 bullous pemphigoid 1127 neurofilaments Ig- AGM A G M SJÖGREN’S SYNDROME 135 oral mucosa Behçet’s/ Crohn’s dis. 1128 GFAP (glial fibrillary acidic protein) 139 exocrine pancreas 1503 basal membrane (urinary bladder) 1129 non-medullated nerves 1391 pancreas acini 1509 epidermal keratin 112f astrocytes 1393 pancreas excretory ducts 191 endomysium GSE, Duhring’s dis. 112g basal ganglia 142 salivary glands (parotid gland) 3011 gliadin GSE, Duhring’s dis. 112h ganglion stellatum 1421 parotid gland acini 1502 herpes gestationis factor 112i plexus myentericus 1423 parotid gland excretory ducts 1504 melanocytes 112j synaptophysin 141 lacrimal gland 150h hair follicle 1130 ganglioside profile GM1, GM2, GM3, GD1a, GD1b, GT1b, GQ1b Sjögren’s syndrome Ig- AGM A G M EYE 1131 GM1 151 ANA (cell nuclei) IF global testing 1178 recoverin 1132 GM2 1595 SS-A (Ro) 1177 tunica choroidea chron. chorioretinitis 1133 GM3 1597 SS-B (La) 1171 cornea 1134 GD1a 1576 ssDNA (single-stranded DNA) 1172 retina 1135 GD1b 1173 lens oculi 1136 GT1b further antibodies 1174 corpus ciliare 1137 GQ1b 1401 prostate 1175 eye muscles 1155 neurofascin 1406 mamma 1176 retro bulbar connective tissue 151 ANA (cell nuclei) IF global testing other: 213 Borrelia burgd.: serum CSF Ig- AGM A G M HEART 1119 CV2 (oligodendrocytes) 1627 AMA-M7 (myocard-specific) 120 cANCA* (granulocytes) Wegener’s dis. Ig- AGM A G M SKELETAL MUSCLE, THYMUS 146 heart muscle 151 ANA (cell nuclei) IF global testing 1435 acetylcholine receptors M. gravis 1462 heart: intercalated disk 1434 MuSK M. gravis 1463 heart: myolemma Ig- AGM A G M IMMUNOHAEMATOLOGY 1437 calcium channels type N LEMS 124 erythrocytes (global testing) 1438 calcium channels type PQ LEMS 1209 granulocyte membrane 1439 potassium channel ab (VGKC) Ig- AGM A G M LIPODYSTROPHY 1221 lymphocytes 144 thymus M. gravis, thymoma 147 lipocytes 1231 thrombocytes: indirect test (free ab) 1431 titin M. gravis 1232 thrombocytes: direct test (bound ab)** 143 skeletal muscle M. gravis 1361 H+/K+-ATPase ab ELISA 1432 sarcolemma Ig- AGM A G M ANTIBODIES AGAINST ANIMAL IgG 1361 PCA (parietal cells) 1436 myosin 3811 HAMA (human anti-mouse IgG) —17— Grey: standard *) ANCA diagn. in acute cases within 1 h **) Special procedure for taking sample ***) CV2 partial protein, which only contains the N-terminally localised epitopes of the antigen

Produktkatalog2010.p65 17 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Antibodies for Infectious Serology

Techniques for the Serological Antibodies against Investigation of Antibodies t t s s i i t ac t ac i i s s t i t i t t t t a a i l tr i l tr a a s ac s ac i i n n t t i i i i rthr rthr s s a a i a a i t y t y i i c c den den ted hep ted hep tory tr lmology tory tr lmology ntest n ntest n a rd a i rd i a a a ous a ous a a i r i r cia i t cia i t ca ca s s c nthem i c nthem i t stro t stro e a e i a i f f a a Ophth Ot STD Pregn CNS Myo Asso IFT ELISA Westernblot EUROLINE Resp Ex Lymph G In Ophth Ot STD Pregn Asso G IFT ELISA Westernblot EUROLINE Resp Ex CNS Myo In Lymph Ig- AGM A G M BACTERIA A-Z Ig- AGM A G M VIRUSES A-Z 219a AÞ pia felis* 2680 Adenovirus type 3 219b Bartonella henselae 2730 Coxsackievirus type 219d Bartonella quintana B1 B2 B3 B4 B5 2055 Bordetella parapertussis B6 A7 A 9 A16 A24 2050 Bordetella pertussis 2570 Cytomegalovirus 2131 Borrelia afzelii Avidity determination 2132 Borrelia burgd. s. stricto 275a Echovirus type 7 CSF diagnostics 2791 Epstein-Barr virus 2133 Borrelia burgd. (USA) capsid Ag (EBV-CA) 2134 Borrelia garinii Avidity determination 2092 Campylobacter coli 2795 Epstein-Barr virus 2091 Campylobacter jejuni early Ag (EBV-EA) 2192 Chlamydia pneumoniae 2793 Epstein-Barr virus 2191 Chlamydia trachomatis nuclear Ag (EBNA) 2040 Diphtheria toxoid 2531 HSV-1 2070 Haemophilus infl uenzae 2532 HSV-2 2080 Helicobacter pylori 2511 HIV-1* 2101 Klebsiella pneumoniae 2512 HIV-2* 216a Legionella bozemanii 2536 Human herpes virus 6 2167 Legionella dumoffi i (HHV-6) 2166 Legionella gormanii 2691 Infl uenza virus type A 2165 Legionella jordanis H1N1 H3N2 2168 Legionella longbeachae 2692 Infl uenza virus type B 2169 Legionella micdadei 2610 Measles virus 2150 Legionella pneumophila CSF diagnostics Serotypes ...... 2630 Mumps virus 2140 Listeria monocytogenes CSF diagnostics 1/2a 4b 2720 Parainfl uenza virus type 2201 Mycoplasma hominis 1 2 3 4 2202 Mycoplasma 2670 Respiratory syncytial pneumoniae virus (RSV) 2060 Tetanus toxoid 2590 Rubella virus 2 111 Treponema pallidum Avidity determination CSF diagnostics CSF diagnostics 2205 Ureaplasma urealyticum 2661 TBE virus 2170 Yersinia enterocolitica 2650 Varicella zoster virus O:3 O:4 O:6 O:9 Avidity determination

Ig- AGM A G M PARASITES A-Z Ig- AGM A G M FUNGI A-Z 2320 Echinococcus gran. 2861 Candida albicans 2231 Leishmania donovani 2862 Candida glabrata 2261 Plasmodium vivax 2863 Candida krusei 2264 Plasmodium falciparum 2865 Candida parapsilosis 2410 Toxoplasma gondii 2864 Candida tropicalis Avidity determination 2841 Saccharom. cerevisiae

Grey: standard analyses *) Currently not available as IVD in the European Union SI IUKA /

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Produktkatalog2010.p65 18 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Antibodies for Allergology Allergen Profiles: Antibodies of class IgE against GLOBAL TEST FOOD ATOPY, POLLEN-ASSOCIATED FOOD ALLERGIES 3840 Determination of total IgE (ELISA) 3410 Allergy Profile Food (f1, f75, f2, f45, f4, f5, f9, f13, f14, f17, f20, f49, 3710 Allergy Profile Atopy f84, f237, f25, f31, f35, f85, f3, f23, CCD) (g6, g12, t3, w6, d1, e1, e2, e3, m2, m6, f1, f2, 3410 Allergy Profile Food 2 f3, f4, f9, f14, f17, f31, f35, f49, CCD) INHALATION (f1, f75, f2, f78, f4, f5, f14, f10, f13, f17, f20, f49, 3710 Allergy Profile Atopy 3 f84, f95, f25, f31, f35, f85, f3, f23, CCD) (g6, t3, t4, w6, d1, d2, e1, e2, e3, m2, m3, f1, 3110 Allergy Profile Inhalation 3411 Allergy Profile Food "South East Asia 1" f75, f2, f3, f4, f13, f14, f31, f49, CCD) (g1, g3, g6, g12, t2, t3, t4, t7, w1, w6, w9, (f1, f75, f2, f4, f9, f10, f14, f13, f17, f63, f64, f83, 3711 Allergy Profile Pollen-Food d1, d2, e1, e2, e3, m1, m2, m3, m6, CCD) fs10, fs14, f23, f24, f80, f179, f105, f336, CCD) Cross Reactions Investigation of Antibodies

3110 Allergy Profile Inhalation 2 3411 Allergy Profile Food "South East Asia 2" (g6, t3, w6, f4, f5, f13, f17, f20, f48, f89, Techniques for the Serological (g6, g12, t2, t3, t4, w6, w9, d1, d2, e1, e2, e3, e6, (f1, f75, f2, f4, f9, f10, f14, f13, f17, f63, f340, f83, f271, f275, f44, f49, f348, f237, f328, f31, e82, e84, es4, m1, m2, m3, m6, CCD) fs10, fs14, f23, f24, f80, f179, f105, f336, CCD) f35, f85, CCD) 3111 Allergy Profile Pediatric Inhalation 3414 Allergy Profile Food "China" 3712 Allergy Profile Pediatrics (g6, g12, t2, t3, t4, w6, w8, w9, d1, d2, e1, (f1, f2, f4, f7, f27, f88, fs35, f13, f14, fs40, f25, (gx, t3, w6, d1, e1, e2, e3, m2, m6, f1, f75, f3, f2, e2, e3, e6, e82, e84, m1, m2, m3, m6, CCD) f292, fs42, f23, f234, f3, f41, f56, fs41, fs77, CCD) f76, f77, f78, e204, f4, f9, f14, f13, f17, f31, f35, 3112 Allergy Profile Mediterranean Inhalation 3415 Allergy Profile Food "Middle East" f49, CCD) (g2, g6, t3, t4, t9, t11, t23, t210, w1, w6, w9, w19, (f1, f75, f2, f78, e204, f4, f14, f45, f13, f17, f20, 3713 Allergy Profile Atopy "China" d1, d2, d70, e1, e2, e3, m2, m6, CCD) f33, f49, f92, f25, f31, f85, f48, f88, f89, CCD) (ts20, w1, w6, ds1, h1, e1, e2, i6, ms1, u80, f1, f2, 3113 Allergy Profile Inhalation "South East Asia" 3416 Allergy Profile Food "Gulf" f13, f14, f27, f88, fs33, fs34, f23, f234, CCD) (ts19, t104, t19, t223, gs1, ds1, i6, u134, e1, (f1, f75, f2, f105, f4, f14, f45, fs36, f13, f29, f33, 3713 Allergy Profile Atopy "China 3" e2, es172, e6, e71, e82, e84, ms1, ms4, m5, f44, f93, f25, f31, f48, f83, f88, f3, f23, CCD) (ts22, w6, us1, ds1, es1, h1, ms5, f245, m12, m45, CCD) 3417 Allergy Profile Food "Cyprus 1" fs9, fs43, fs56, fs34, fs44, CCD) 3116 Allergy Profile Inhalation "China" (f1, f2, f75, f76, f77, f78, f81, f4, f45, f5, f14, f7, 3719 Allergy Profile Atopy “Mix Screen Turkey 1” (gs23, ts21, t3, t8, t11, t12, t14, t70, ws18, w1, w6, f79, f9, f10, f13, f144, f17, f20, f49, CCD) (hs12, ms1, gs2, ws21, ts26, ts25, fx5, fx20, w9, es1, d1, d2, i6, ms5, m1, u73, u80, CCD) 3418 Allergy Profile Food "Cyprus 2" es5, es6, es172, es2, CCD) 3117 Allergy Profile Inhalation "Middle East" (f177, f23, f234, f24, f258, f3, f37, f40, f41, f80, f48, 3719 Allergy Profile Atopy “Turkey 1” (g1, g6,g12, t2, t3, t7, t9, w1, w6, w8, d1, d2, f108, f132, f212, f25, f292, f31, f35, f47, f96, CCD) (d1, m2, es5, g6, t3, w6, f1, f2, f13, i6, e1, e84, m1, m2, m3, m5, m6, CCD) 3419 Allergy Profile Food "Cyprus 3" f14, f4, fs16, CCD) 3118 Allergy Profile Inhalation "Gulf" (f26, f63, f83, f88, f237, f29, f32, f328, f33, f44, f49, (g6, g12, t2, t3, t7, t9, w1, w6, d1, d2, i6, e1, f72, f84, f95, f281, f86, f89, f90, f105, f93, CCD) e2, e3, e17, m1, m2, m3, m5, m6, CCD) 3420 Allergy Profile Food “Mix Screen Turkey 1” 3119 All. Profile Inhalation “Mix-Screen Turkey 1” (f245, fs8, fs50, fs38, fs37, fs46, fs47, fs48, (ts23, ts24, ts25, gs12, gs15, gs21, ws17, ws18, fs49, fs45, fs10, fs16, CCD) ws19, ws20, ms11, ms12, CCD) 3420 Allergy Profile Food “Turkey 1” 3119 Allergy Profile Inhalation “Turkey 1” (f1, f75, f2, f169, f78, f4, f79, f9, f14, f10, f13, f17, (gs12, gs15, gs21, g12, ts23, ts24, t9, t70, ws18, f144, u87, f222, f73, f33, f44, f49, f92, f84, f146, ws19, ws20, d1, d2, i6, es2, es172, e1, e2, e3, e4, f328, f25, f31, f35, f48, f95, f97, f122, f132, fs14, e80, e81, e84, ms11, ms12, m1, m2, m3, m6, CCD) fs10, fs43, f83, CCD) 3119 Allergy Profile Inhalation “Turkey 2” 3420 Allergy Profile Food “Turkey 2” (m1, m2, m3, m6, ds1, i6, e1, e2, e3, e4, (f3, f21, f206, f437, f438, f436, f71, f177, f324, INSECT VENOMS e81, e84, CCD) f27, f83, f88, CCD) 3120 Allergy Profile Inhalation "India" 3420 Allergy Profile Food “Turkey 3” 3720 Allergy Profile (g6, g12, g20, t18, w4, w27, w29, ds1, d2, i6, e1, e2, (f1, fs51, f14, fx20, f13, fs35, f49, f44, f25, f31, Insect Venoms e11, e85, m3, m37, u81, u126, u129, u140, CCD) fs10, fs16, CCD) (i1, i3, CCD) 3421 Allergy Profile Food "India" (f2, f75, f168, f4, f9, f14, f13, f36, f49, f50, f35, f38, f48, f244, f83, f89, f74, f240, f23, f24, CCD)

Allercoat™ 6 System: Antibodies of class IgE against 600 different allergens of the areas animal allergens, environmental allergens, food, grasses, herbal and flower pollen, house dust, insects, mites, moulds, parasites, pharmaceutical drugs, trees.

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Produktkatalog2010.p65 19 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological EUROIMMUN Microplate ELISA Investigation of Antibodies

stain Principle of the Test • Polystyrene microplate strips coated with purified, biochemically characterized chromogen substrate antigens are used as solid phase containing bound antigens. POD • If the sample is positive, specific antibodies in the diluted serum sample attach to the antigens coupled to the solid phase. POD-labelled anti-human antibody • In a second step, the attached antibodies are detected with peroxidase-labelled anti-human antibodies. POD • In a third step, the bound antibodies are made visible using a chromogen/ substrate solution which is capable of promoting a color reaction. The intensity of the color produced is proportional to the concentration of antibodies in the serum sample. • Monospecific ELISA (enzyme immunoassays with a single antigen) provide a quantitative in vitro assay for the detection of antibodies. specific human antibody • “Profile ELISA” provide a semiquantitative in vitro assay for the detection of different antibodies on a single microplate strip. • The solid phase of “Pool ELISA” is coated with an antigen mixture for the semi- antigen-coated quantitative detection of antibodies whose specificity must be subsequently microplate well investigated by monospecific assays.

Reliable and Economical Calibration/Evaluation • In the case of a quantitative ELISA, calibration is performed using three cali- bration sera. Calibration serum 1: upper limit of the measurement range Calibration serum 2: upper limit of the normal range (cut-off value) Calibration serum 3: negative • Only three wells are required for calibration, followed by serum samples. There is no need to incubate blank values or duplicate determinations. • Semiquantitative ELISA are performed using only one calibrator. • The calibration is performed in relative units per milliliter (RU/ml) or, if an international reference serum exists, in international units per milliliter (IU/ml). • Each test can be optionally performed using a positive or negative control serum included in the test kit. Kit-specific reference ranges are provided for each calibrator and control serum. • All calibrations can be easily performed with the usual ELISA software.

Easy, Quick and Economical Handling A • Microplate strips containing break-off wells (except Profile ELISA), each marked B with an antigen abbreviation to avoid confusion of wells. C • Reagents ready for use (wash buffer: concentrate). Reagents are color-coded to D ensure positive identification. dark red: calibration serum 1 orange: anti-human IgA POD-conj. E red: calibration serum 2 green: anti-human IgG POD-conj. F light red: calibration serum 3 red: anti-human IgM POD-conj. G dark blue: pos. control serum turquoise: anti-human IgGM POD-conj. H green: neg. control serum yellow: anti-human IgAGM POD-conj. 1 2 3 4 5 6 7 8 9 10 11 12 light blue: sample buffer • The sample buffer for infectious serology ELISA (detection of antibodies of class IgM) already contains an IgG/RF absorbent.

• Several tests can be combined on one and the same microplate, since the incu- H. PYL. H.

H. PYL. H. bation times (30 min; 30 min; 15 min) are identical for all ELISA. Incubation at H. PYL. H.

H. PYL. H. room temperature.

H. PYL. PYL. H. H.

H. PYL. H. PYL. H. PYL. H. PYL. H. PYL. • Compatible with all commercial washer and reader systems.

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Produktkatalog2010.p65 20 30.10.2009, 09:00 Medizinische Labordiagnostika EUROIMMUN AG

EUROIMMUN Microplate ELISA

Determination of Low-Avidity Antibodies • An alternative principle for the serological diagnosis of fresh infections has been established by investigating the antibody avidity. • The first reaction of the immune system following an infection is the formation of low-avidity antibodies. As the infection proceeds, increasingly antigen-adapted 10 E IgG is formed, and avidity grows. As long as high-avidity IgG is not yet detected with urea

8 RAI = Investigation of Antibodies Ewithout urea in the serum, it can be assumed that the infection is still in an early stage. Techniques for the Serological 6 • To identify low-avidity antibodies in a patient’s serum, two microplate ELISA are Primary Infection

performed in parallel: one test is carried out in the conventional way, the other Previous Infection 4 one includes urea treatment between incubations with patient’s serum and per-

oxidase-labelled anti-human IgG, resulting in the detachment of low-avidity Number of Patients 2 antibodies from the antigens. 0 • Low-avidity antibodies are present if the ELISA extinction is significantly reduced 0 255075100 by urea treatment. For an objective interpretation, the relative avidity index (RAI) Relative Avidity Index (RAI) in % can be calculated out of the measured values with and without urea incubation. • Serum dilution 1 : 100, conjugate class anti-human IgG, POD-labelled. Avidity of antibodies against EBV-CA (IgG) • 3-point calibration, quantitative (IgG). • The following test kits for avidity determination are available: Toxoplasma gondii, CMV, rubella virus, VZV, West-Nile virus, EBV-CA.

123456 CA C3 A Antibody Determination in CSF 1:2 CB S3 B • Indication: local infections of the brain. 1:401 CC C4 C • CSF dilution 1 : 2, serum dilution 1 : 404. Conjugate classes anti-human IgG or 1:2 CD S4 IgM, POD-labelled. D 1:401 C1 C5 • Easy to conduct: ready-for-use reagents. E 1:2 1:2 S1 S5 • 4-point calibration, quantitative. Identical incubation conditions and times (room F temperature; 60 min / 60 min / 15 min): all EUROIMMUN ELISA for CSF dia- 1:401 1:401 C2 C6 G gnostics can be combined without difficulty on one and the same microplate. 1:2 1:2 S2 S6 H • The antibody concentration in the patient’s serum is determined in parallel to 1:401 1:401 the antibody concentration in CSF on one and the same microplate. The CSF/ CA-D CSF calibratorsC CSF S serum serum quotient CSQpath.-spec. is calculated from both measured values. • An intrathecal synthesis of specific antibodies is present if the CSF/serum ELISA incubation scheme

quotient of the specific antibodies CSQpath.-spec. is significantly higher than the CSF/serum quotient of the whole IgG (CSQtotal) or if necessary the CSQlim.. The relation of both values indicates the relative CSF/serum quotient CSQrel. (synonym: antibody specificity index, ASI). • Interpretation of results (according to the recommendations of Prof. Reiber):

CSQrel. < 1,3: standard range

CSQrel. 1,3 – 1,5: borderline range

CSQrel. > 1,5: Indication of pathogen-specific antibody production in the CNS

• For the automatic calculation of the CSQrel. EUROIMMUN provides a specific Excel table free of charge. • Highest sensitivity, specificity and reproducibility. Antibody concentrations in the serum and CSF are determined within the linear range of the test. • The following test kits for CSF diagnostics are available: Borrelia burgdorferi, Table-based evaluation of the CSQ Toxoplasma gondii, HSV-1, HSV-2, HSV-1/2 Pool, CMV, rubella virus, measles rel. virus, mumps virus, VZV, TBE, EBV-CA. • All test systems for CSF diagnostics can also be used only for serology. • Perfectly adapted for the automated incubation in incubation devices.

Reference range for normal values, intact blood-CSF barrier function Blood-CSF barrier dysfunction, no Ig production in CNS

total Blood-CSF barrier dysfunction, additional Ig production in CNS

CSQ Clear Ig production in CNS, no disturbance in blood-CSF barrier function Error in blood extraction or analysis

CSQalb.

CFS/serum quotient diagram according to Reiber and Lange (1991)

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Produktkatalog2010.p65 21 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological ELISA Automation Using the EUROIMMUN Analyzers Investigation of Antibodies

EUROIMMUN Analyzer I and EUROIMMUN Analyzer I-2P: Broad Parameter Spectrum, Proven Reliability, Variable Throughput • One for all: fully automated processing of all EUROIMMUN ELISA – autoimmune diagnostics, infectious serology and allergology – with only one system • Flexibility for your benefit: open system with more than 800 validated EUROIMMUN parameters for serum, plasma and cerebrospinal fluid, over 50 or 30 parameters in parallel. • Convenient, simple and reliable operation: e.g. by scanning QC certificates using a 2D-hand barcode scanner – ready-for-use reagents and preprogrammed assay protocols enable you to start immediately. • Capacity and throughput: quick loading and efficient time management allow processing of up to 70 or 50 tests per hour – up to 7 or 3 plates, 180 or 144 samples at the start of a run. • Security for patients: validated test systems and the comprehensive safety kit provide the basis for reliable diagnostics. • Reliability and service: instruments and reagents from one manufacturer, quick and targeted support from our personnel for a smooth workflow in your laboratory.

Modular System: A Highly Sophisticated Solution • High convenience, fast and reliable loading through barcode identification of samples and reagents: automatic scanning when racks are inserted, reading of lot-specific QC data via 2D hand barcode scanner. • Dilution area: 288 or 192 dilution positions (Deepwell, 2 ml). • Liquid level detection (capacitive), multi-shot (dispensing) mode, automatic tip detection, clot detection. • Pipetting possible during plate transport due to separation of transport and pipetting unit. • 4 or 2 incubators with heating and shaking function, 4 or 3 incubators at room temperature. • Standard Windows software: familiar user interface, all relevant statistical functions provided, available in different languages. • Efficient use and convenient handling of tips and dilution plates through memory function.

A Convincing and Reliable Package: EUROIMMUN Analyzer, EUROIMMUN ELISA, EUROIMMUN Service • Comprehensive test system validation for the EUROIMMUN Analyzer: all para- meters validated in accordance with the 98/79/EC directive and based on EN ISO 13485:2003/CMDCAS. • All ELISA test systems are manufactured according to the European Quality Standards (IVD). • National and international conformity (standardisation): CE, IVD, FDA and CMDCAS. • Programming and set-up of automated system, including introduction to the system with customer training, performed by qualified personnel. oved pr p • Reliable and fast delivery of consumables and reagents. a

• Connection to in-house computer system via communication protocol ASTM.

a • Maintenance contract with EUROIMMUN on request.

p

p

r

o d v e *) soon available for the EUROIMMUN Analyzer I-2P

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Produktkatalog2010.p65 22 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

Incubating the Microplate ELISA

microplate wells coated with antigens Investigation of Antibodies diluted Techniques for the Serological Pipette: 100 µl per well samples

Incubate: 30 min

Wash: 300 µl wash buffer per well 3x

enzyme conjugate Pipette: 100 µl per well

Incubate: 30 min

Wash: 300 µl wash buffer per well 3x

chromogen/ Pipette: 100 µl per well substrate solution

Incubate: 15 min

yyy


yyy

yy

stop Pipette: 100 µl per well solution

yy

yyy


yyy

yy

yyy


yyy

yy

Evaluate: photometric measurement


yyy


yyy

yy

at a wavelength of 450 nm


yyy


yyy

yy

yyy


yyy

yy

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Produktkatalog2010.p65 23 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological EUROASSAY: Line Blot in TITERPLANE™ Technique Format

Investigation of Antibodies yyyyyy Principle of the Test membrane coated • Membrane strips coated with thin parallel lines of several purified, biochemically with antigen characterized antigens are used as solid phase. The membrane strips are fixed as BIOCHIPs in the fields of microscope slides. specific human antibody • If the sample is positive, specific antibodies in the diluted serum sample attach to the antigens coupled to the solid phase. • In a second incubation step, the attached antibodies react with AP-labelled anti- human antibodies. • In a third step, the bound antibodies are stained with a chromogen/substrate solution which is capable of promoting a color reaction. An intense dark band at AP the line of the corresponding antigen appears if the serum sample contains specific antibodies. AP-labelled anti-human • The microscope slides are incubated using the TITERPLANE™ Technique: antibody samples and reagents are applied to the reaction areas of a reagent tray. The AP slides are then placed into the recesses of the reagent tray, where all test strips of one slide come into contact with the liquids, and the individual reactions chromogen substrate begin simultaneously. • Depending on the spectrum of antigens used, it is possible to analyze several antibodies next to each other and simultaneously under identical conditions. stain

Easy Handling • Several serum samples can be analyzed simultaneously on one and the same slide. • Total time for performing the EUROASSAY test is about 100 minutes. During the washing procedure, reagents for the next incubation step can be applied to reagent trays. • All incubation steps proceed at room temperature. Shaking the slides together with the reagent tray on a circulatory shaker ensures the best possible sensitivity. • Low reagent consumption. Only 50 µl each of diluted serum and reagent are needed per test field. • Reagents ready for use (wash buffer: concentrate).

Reliable and Simple Evaluation • Since results are evaluated visually, there is no investment required for photometers, etc. • The antigen bands are located at exactly defined positions, which means that evaluation of the test is much simpler than for Westernblots. • Correct completion of the individual incubation steps in each test field is nRNP/Sm Scl-70 indicated by staining of the control band. • Positive and negative results can be easily and reliably differentiated from each Sm Jo-1 other. The intensity of the antigen bands correlates with the antibody titer. SS-A • The antigens used are highly pure, mostly isolated by affinity chromatography. The membrane strips do not contain any superfluous proteins which might Control SS-B cause unspecific positive results. band • The incubated microscope slides can be stored for long periods. Results can be easily documented.

EUROASSAY Anti-ENA ProfilePlus: detection of antibodies against SS-A and SS-B in a case of Sjögren’s syndrome.

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Produktkatalog2010.p65 24 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

Incubating the EUROASSAY (TITERPLANE™ Technique)

slide

membrane strips reagent tray Investigation of Antibodies Techniques for the Serological

Pipette: 50 µl per field

diluted samples

Incubate: 30 min shaking on a

circulatory shaker (300 rpm)

Wash: 5 s flush wash 15 min cuvette buffer

Pipette: 50 µl per field enzyme conjugate

Incubate: 30 min shaking on a

circulatory shaker (300 rpm)

Wash: 5 s flush wash 15 min cuvette buffer

chromogen/substrate Pipette: 50 µl per field solution

Incubate: 10 min shaking on a

circulatory shaker (300 rpm)

Wash: flush with deionized or distilled water, air dry

Evaluate: visual assessment of color intensity

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Produktkatalog2010.p65 25 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological The EUROLINE: A New Technique for Extensive Antibody Profiles Investigation of Antibodies

stain Principle of the Test • Membrane strips coated with thin parallel lines of several purified, biochemically chromogen substrate characterized antigens are used as solid phase. The membranes are fixed as AP BIOCHIPs onto synthetic foil. AP-labelled • If the sample is positive, specific antibodies in the diluted serum sample attach anti-human to the antigens coupled to the solid phase. antibody • In a second incubation step, the attached antibodies react with alkaline- AP phosphatase-labelled anti-human antibodies. • In a third step, the bound antibodies are stained with a chromogen/substrate solution which is capable of promoting a color reaction. An intense dark band at the line of the corresponding antigen appears if the serum sample contains specific antibodies. specific human • Depending on the spectrum of antigens used, it is possible to analyze several antibody antibodies next to each other and simultaneously under identical conditions.

membrane coated with antigen

yyyyyy

Easy Handling, Reliable and Simple Evaluation • A separate membrane strip is incubated for each serum sample. nRNP/Sm Mi-2 AMA M2 • Total time for performing the analysis is about 105 minutes. Sm • The incubation can be automated using the EUROBlotMaster. M2-3E Ku • All incubation steps proceed at room temperature. (BPO) SSA • The antigen bands are located at exactly defined positions, which means that Ro-52 PM-Scl100 the evaluation of the test is much simpler than for Westernblots. Sp100 SS-B • Correct completion of the individual incubation steps is indicated by staining of PM-Scl75 the control band on each EUROLINE test strip. Scl-70 • Positive and negative results can be easily and reliable differentiated from each PML other. The intensity of the antigen bands correlates with the antibody titer. PM-Scl Jo-1 • The antigens used are highly pure, mostly isolated by affinity chomatography. The membrane strips do not contain any superfluous proteins which might gp210 Jo-1 SRP cause unspecific positive results. • The incubated EUROLINE test strips can be stored for long periods. Results can CENP B be easily documented. PL-7 LKM-1 • The program EUROLineScan from EUROIMMUN has been developed to enable PCNA quantitative evaluation of EUROLINE test strips, to facilitate management of PL-12 data, and to provide detailed documentation of results. First, the incubated LC-1 dsDNS EUROLINE test strips are scanned using a flatbed scanner. EUROLineScan Nucleos. recognizes the position of the strips, even if they have been placed inexactly, EJ identifies the bands, and measures their intensity. The results are then saved Histones together with the image data. A separate results sheet can be produced for each SLA/LP patient. Rib. P-prot. OJ

Ro-52 AMA-M2 Ro-52

Control Control Control

Incubated EUROLINE test strips (Autoimmune Liver Diseases Profile, ANA Profile 3, Myositis Profile 3.

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Produktkatalog2010.p65 26 30.10.2009, 09:02 Medizinische Labordiagnostika EUROIMMUN AG

EUROLINE Automation Using EUROBlotMaster and EUROLineScan

EUROBlotMaster • Standardised incubation of immunoblot strips – higher precision and repro- ducibility. • Automatisation of all EUROIMMUN immunoblot strips (EUROLINE, EUROLINE- WB, Westernblot)

• Over 65 validated parameters available (16 autoantibody, 28 infectious and 21 Investigation of Antibodies allergy parameters) Techniques for the Serological • Up to 30 strips per test run • Easy operation • Combination of different conjugates/tests in one run • Walk-away function – fully automated from the start to the end of processing following loading • Compatible with modern evaluation systems such as EUROBlotCamera and EUROBlotMaster EUROLineScan

Automatic Evaluation of the Results Using EUROLineScan • For all EUROIMMUN blot systems: EUROLINE, EUROLINE-WB, Westernblot. • For all areas: autoimmune diagnostics, infectious serology and allergology. • EUROBlotCamera: digitalisation of strips while in the incubation tray. • EUROBlotScanner: digitalisation of strips using flatbed scanner. • Fully automated identification, quantitation and assignment of bands. • Option to modify results (changes are automatically documented). • Complete results obtained just a few minutes after finishing the incubation. • Fully automated administration and documentation of extensive individual data. • Electronic archiving of all images and data (avoids the need to store potentially infectious blot strips). EUROBlotCamera EUROBlotScanner • Online connection to laboratory software. • Network compatible.

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Produktkatalog2010.p65 27 30.10.2009, 09:03 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological Westernblot/EUROLINE-WB: Reliable Differentiation of Antibodies Present Investigation of Antibodies

stain Principle of the Test • Membrane strips containing electrophoretically separated antigen extracts are chromogen substrate used as solid phase. The position of the proteins depends on their respective AP molecular masses. AP-labelled • If the sample is positive, specific antibodies in the diluted serum sample attach anti-human to the antigens coupled to the membrane. antibody • In a second incubation step, the attached antibodies react with AP-labelled anti- AP human antibodies. • In a third step, the bound antibodies are stained with a chromogen/substrate solution which is capable of promoting a color reaction. An intense dark band at the line of the corresponding antigen appears if the serum sample contains specific antibodies. specific human • Evaluating the band patterns on the incubated membrane strips involves antibody differentiating non-specific from specific antibodies. The number and intensity of the specific bands is decisive for the result “positive/negative“.

membrane coated with antigen

yyyyyy

Easy Handling, Reliable Evaluation and High Diagnostic Sig- nificance VlsE antigen on EURO- LINE membrane chip • A separate membrane strip is incubated for each serum sample. • Total time for performing the Westernblot test is about 115 minutes. • All incubation steps proceed at room temperature. p 83 • The bands are assigned according to a lot-specific evaluation matrix provided. A separate lot is issued for each electrophoresis gel, helping to avoid errors in the assignment of the bands. • Every test kit contains a membrane strip of the same lot incubated with a positive reference serum. Therefore, there is no need to incubate a positive control serum. • The membrane strips are pre-numbered to prevent confusion. Laborious labelling is not necessary. p 41, Flag. • Correct completion of the individual incubation steps for each membrane strip is p 39, Bmp A indicated by staining of the control band at the bottom of the strip. • Positive and negative reactions can be easily and reliably differentiated from each other. The intensity of the antigen bands correlates with the antibody titer. • The Westernblot is the method of choice when the objective is to confirm or p 31, Osp A differentiate positive results obtained in a screening test (indirect immuno- p 30 fluorescence or microplate ELISA). • EUROLINE-WB is a combination of westernblot and line blot techniques. Proteins from a whole antigen extract are electrophoretically separated according to molecular mass and transferred onto a nitrocellulose membrane. Highly purified native or recombinant antigens are then printed as lines onto the p 25, Osp C westernblot strips (EUROLINE membrane chip). • The program EUROLineScan from EUROIMMUN has been developed to enable p 21 quantitative evaluation of Westernblot/EUROLINE-WB test strips, to facilitate management of data, and to provide detailed documentation of results. First, p 19 the incubated Westernblot/EUROLINE-WB test strips are scanned using a flatbed p 17 scanner. EUROLineScan recognizes the position of the strips, even if they have been placed inexactly, identifies the bands, and measures their intensity. The Alignment bar results are then saved together with the image data. A separate results sheet can be produced for each patient.

EUROLINE-WB Borrelia Control band

EUROLINE-WB: detection of antibodies against Borrelia.

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Incubating the EUROLINE/Westernblot/EUROLINE-WB using the EUROBlotMaster or manually on a rocking platform

membrane strip incubation channel

buffer Investigation of Antibodies

Pipette: 1.5 ml per channel Techniques for the Serological

Incubate: 5-15 min shaking, de- pending on test system

Aspirate off:

diluted samples

Pipette: 1.5 ml per channel

Incubate: 30 min shaking

Wash: 1.5 ml buffer, buffer 5 min incubation, aspirate off 3x enzyme conjugate

Pipette: 1.5 ml per channel

Incubate: 30 min shaking

Wash: 1.5 ml buffer, buffer 5 min incubation, aspirate off 3x chromogen/substrate solution

Pipette: 1.5 ml per channel

Incubate: 10 min shaking

Wash: rinse with distilled water, aspirate off

Evaluate: with EUROLineScan or visual assessment

Applicable for most EUROLINE/Westernblot/EUROLINE-WB test kits —29—

Produktkatalog2010.p65 29 30.10.2009, 09:03 Medizinische Labordiagnostika EUROIMMUN AG

Techniques for the Serological EUROIMMUN Radioimmunoassays (RIA/IRMA) Investigation of Antibodies

Test principle RIA (precipitation techniques) • In the first incubation step patient sera are incubated with 125I-labelled antigen in radioactively polystyrene tubes. Any specific antibodies in the sera bind to the antigen. labelled specific human antibody antigen • In the second incubation step the antigen-antibody complexes are precipitated (“tracer”) using a precipitation agent. • The precipitate is washed with buffer. After centrifugation and decanting of the 125I 125I supernatant, the radioactivity in the precipitate is counted using a gamma counter. The intensity of the radioactivity is proportional to the concentration of specific antibody in the patient serum. • The antibody concentration is evaluated quantitatively using a calibration curve.

Test principle RIA (coated tubes) precipitation agent • RIA tests (coated tubes) are competitive ligand assays for antibody and antigen determinations. • The intensity of radioactive radiation is inversely proportional to the concentration of specific antibodies or antigens in the sample. • The quantitative evaluation of the antigen/antibody concentration is carried out using a calibration curve.

Test principle IRMA (antigen determination)

solid phase • With this test principle, monoclonal antibodies which are bound directly or (tube surface) radioactively indirectly to the inner wall of polystyrene tubes are used. labelled antibody • During the first incubation step, the patient sera to be investigated are incubated with the monoclonal 125I-labelled antibodies in the coated tubes. 125I • The antigen in the sample is bound by the immobilised antibodies and by the 125I-labelled antibodies. This results in a solid-phase bound sandwich complex. analyte • The unbound 125I-labelled antibodies are removed by washing and subsequently decanting. The intensity of radioactive radiation is proportional to the concen- tration of antigens in the patient serum. • The quantitative evaluation of the antigen concentration is carried out using a calibration curve. antibody

Simple and economical handling, reliable analysis • Simple test procedure. • Synchronous processing of samples, including different tests in parallel. • Ready-to-use reagents (possible exceptions: tracer, precipitation reagents). • Different test formats for small and large sample series. • Because of the large measurement range of EUROIMMUN RIA, further measurements with other sample dilutions are generally not necessary. • Simple evaluation of test results. • Each test can be optionally evaluated with controls which are supplied in the test kit. Test kit-specific reference ranges are given for all controls. • EUROIMMUN radioimmunoassays show the following analytical characteristics: – High analytical specificity. – High detection sensitivity. – High clinical sensitivity and specificity. – Good reproducibility.

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Produktkatalog2010.p65 30 30.10.2009, 09:03 Medizinische Labordiagnostika EUROIMMUN AG EUROIMMUN Products for the Determination of Autoantibodies

EUROIMMUN PRODUCTS FOR THE DETERMINATION OF AUTOANTIBODIES

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Autoantibodies against Cell Nuclei (ANA) Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: EUROPLUS™ ANA Mosaic 20 • Screening test for the detection of antibodies against cell nuclei (ANA). • Indications: rheumatic diseases. • Initial dilution 1 : 100; conjugate class anti-human IgG, FITC-labelled. • Using HEp-2 cells many antibodies against cell nuclei can be analyzed, e.g. anti- bodies against DNA, histones, RNA, nRNP, Sm, SS-A, SS-B, nuclear dots, centro- meres, nuclear membrane, nucleoli (PM-Scl, fibrillarin, RNA polymerase I, NOR), Scl-70, cyclin I and II, spindle fibers, midbody, centrioles. • In addition, cytoplasmic autoantibodies are identified with HEp-2 cells: antibodies against ribosomes, Jo-1, mitochondria, Golgi apparatus, actin etc. • The primate liver permits the verification of results between both substrates, makes the pre-differentiation of a large number of ANA possible, and helps to establish titer levels. Moreover, the primate liver often contains additional antigens, allowing EUROPLUS™ ANA Mosaic 20 (HEp-2 cells, pri- the identification of further autoantibodies: antibodies against LMA, LSP, endo- mate liver, SS-A+SS-B BIOCHIPs, rib. P-prot.+Jo-1 mysium, bile ducts and endothelium cells, as well as cANCA und pANCA. BIOCHIPs: antibodies against SS-A/SS-B. • The EUROPLUS™ system is a monospecific test that can be used to confirm the presence of autoantibodies against cell nuclei and cytoplasm with one and the same test kit. The following antigens are currently available as EUROPLUS™ Order No. Formats BIOCHIPs: SS-A, SS-B, nRNP/Sm, Sm, Scl-70, Jo-1, ribosomal P-proteins. FA 1510-####-20 G page 126

Indirect Immunfluorescence Test: Innovative Cell Line from EURO- IMMUN, HEp-20-10 • Screening test for detection of antibodies against cell nuclei. • Indications: rheumatic diseases. • Initial dilution 1 : 100; conjugate class anti-human IgG, FITC-labelled. • Compared to standard HEp-2 cells, HEp-20-10 cells demonstrate 10-fold more mitotic cells. Antibodies against mitotic-specific structures (centromeres, spindle fibers, midbody, centrioles, NOR) can be more easily identified than with con- ventional preparations. • At the same time, the cell line HEp-20-10 offers the full antigen spectrum for cell nuclei antibody diagnostics. • The BIOCHIP with HEp-20-10 can be supplemented with additional substrates, HEp-2010: antibodies against spindle fibers. for example, primate liver (ANA; Order No. FA 1512-####-1 G) as well as rat kidney and rat stomach (Order No. FA 1802-####-3 G).

Order No. Formats FA 1522-#### G page 128

EUROASSAY: Anti-ENA ProfilePlus • Differentiation of anti-nuclear antibodies (ANA). • Indications: rheumatic diseases. • Serum dilution 1 : 100; conjugate class anti-human IgG, AP-labelled. • 6 relevant anti-nuclear antibodies against “extractable nuclear antigens“ (ENA) can be detected simultaneously and monospecifically: antibodies against nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1. • Native antigens, purified by affinity chromatography. • On request EUROASSAY can be produced with special antigen combinations, for example, with dsDNA, histones, nucleosomes, PM-Scl, nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, Jo-1, ribosomal P proteins, centromere protein B, M2, M4, M9, SLA/LP, LC-1, LKM-1. Incubated EUROASSAY Anti-ENA ProfilePlus.

Order No. Formats DA 1590-####-1 G page 79

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Autoantibodies against Cell Nuclei (ANA)

EUROLINE: ANA Profile 3 nRNP/Sm Sm • Differentiation of antibodies against cell nuclei (ANA). SS-A Ro-52 • Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’s SS-B syndrome, progressive systemic sclerosis, poly/dermatomyositis, PBC. Scl-70 • Serum dilution 1 : 100; conjugate class anti-human IgG, AP-labelled. PM-Scl Jo-1 • With the EUROLINE ANA-Profile 3, fifteen autoantibodies can be determined: CENP B antibodies against nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, PCNA dsDNA centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P- nucleos. proteins, AMA M2. histones • Antibodies against SS-A are characteristic markers for SLE and Sjögren’s rib. P-prot.

AMA M2 EUROIMMUN Products for the

syndrome. In contrast, antibodies against Ro-52 also occur in patients with other Determination of Autoantibodies autoimmune diseases. control • Native antigens, purified by affinity chromatography (exception: centromere protein B, PM-Scl, Ro-52, PCNA). • Further antigen combinations: page 80. Incubated EUROLINE ANA Profile 3. • Test strips can be automatically incubated and evaluated using the systems EUROBlotMaster und EUROLineScan (see page 27). Order No. Formats DL 1590-1601-3 G page 80

EUROLINE: Myositis Profile 3 Mi-2 • Differentiation of myositis-associated antibodies against cell-nuclear and Ku cytoplasmic antigens. PM-Scl100 • Indications: poly/dermatomyositis. PM-Scl75 • Serum dilution 1 : 100, conjugate class anti-human IgG, AP-labelled. Jo-1 • With the EUROLINE Myositis Profile 3, eleven autoantibodies can be determined: SRP antibodies against Mi-2, Ku, PM-Scl100, PM-Scl75, Jo-1, SRP, PL-7, PL-12, EJ, OJ PL-7 and Ro-52. PL-12 • Test strips can be automatically incubated and evaluated using the systems EJ EUROBlotMaster und EUROLineScan (see page 27). OJ Ro-52

control

Incubated EUROLINE Myositis Profile 3.

Order No. Formats DL 1530-1601-3 G page 80

EUROLINE-WB: HEp-2 Cell Antigens plus SS-A, Ro-52 and CENP B rec. CENP B native SS-A rec. Ro-52 • Differentiation of antibodies against cell-nuclear and cytoplasmic antigens. CENP B Ku • Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’s RNP 70 syndrome, progressive systemic sclerosis, poly/dermatomyositis, PBC. SS-A Ro-52 • EUROLINE-WB is a combination of westernblot and line blot techniques. Proteins from a whole antigen extract of HEp-2 cells are electrophoretically separated according to molecular mass and transferred onto a nitrocellulose membrane. A RNP A membrane chip coated with highly purified native SS-A, recombinant Ro-52 and Sm B/B’ recombinant CENP B is then added to the westernblot strips.

• Antibodies against SS-A are characteristic markers for SLE and Sjögren’s Rib.-P syndrome. In contrast, antibodies against Ro-52 also occur in patients with other autoimmune diseases. EUROLINE-WB contains both antigens next to each other at defined positions, in addition to the complete HEp-2 antigen spectrum of the Westernblot. The use of native SS-A increases the sensitivity, since 37% of anti- bodies against SS-A do not show any reaction with the denatured antigen from the Westernblot Incubated EUROLINE-WB HEp-2 Cell Antigens plus • Serum dilution 1 : 50, conjugate class anti-human IgG, AP-labelled. SS-A, Ro-52 and CENP B. • Antigens: SDS extract from HEp-2 cells (whole antigen), highly purified native SS-A from calf thymus, recombinant Ro-52 and CENP B. Order No. Formats DW 1520-1601-3 G page 83

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Autoantibodies against Cell Nuclei (ANA) Determination of Autoantibodies

EUROIMMUN Products for the Microplate ELISA: ANA Screen, Anti-ENA PoolPlus • Screening test for predifferentiation of antibodies against cell nuclei (ANA) and cytoplasm components. • Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’s syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis. • Serum dilution 1 : 200, conjugate class anti-human IgG, POD-labelled. • One microplate well incubated per patient. • 1-point calibration, semiquantitative. • Native antigens (exception: centromere, recombinant). • The ANA Screen ELISA supplements the gold standard immunofluorescence. It is based on a mixture of 10 highly purified antigens, which provide higher sensitivity and specificity than the undefined cell extracts used by other Incubated ELISA ANA Screen (antigen mixture of manufacturers. dsDNA, histones, nRNP/Sm, Sm, SS-A, SS-B, Scl- • Two ELISAs with different antigen combinations, adapted to particular 70, Jo-1, ribosomal P-proteins, centromere). indications or for follow-up of immunofluorescence patterns, are available.

Order No. Formats EA 1590-9601-8 G page 87

Microplate ELISA: SLE Profile 1/2, Anti-ENA ProfilePlus 1/2 • Differentiation of antibodies against cell nuclei (ANA) and cytoplasm com- ponents. • Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’s syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis. • Serum dilution 1 : 200; conjugate class anti-human IgG, POD-labelled. • 8 or 6 relevant antibodies can be detected simultaneously. • 1-point calibration, semiquantitive. Calibrator pool and negative controls each on a separate microplate strip (SLE Profiles and Anti-ENA ProfilePlus 2) or on the same microplate strip as the patient serum. • Native antigens (exception: Ro-52, centromere and PM-Scl, recombinant). • In total 4 different ELISAs with different antigen combinations, adapted to Incubated ELISA Anti-ENA ProfilePlus 2 particular indications or for follow-up of immunofluorescence patterns, are (antigens: ribosomal P-proteins, nRNP/Sm, Sm, available. SS-A, SS-B, Scl-70, Jo-1, centromere).

Order No. Formats EA 1590-1208-2 G page 87

Microplate ELISA: ANA Single-Antigen ELISAs • Differentiation of antibodies against cell nuclei (ANA) and cytoplasm com- ponents. • Indications: rheumatic diseases. • Serum dilution 1 : 200; conjugate class anti-human IgG, POD-labelled. • Antibodies against cell nuclei components can be determined quantitatively in RU/ml. • 3-point calibration, quantitative. • Identical incubation conditions and times: all single-antigen tests can be com- bined with each other on one microplate. • Native antigens (exceptions: centromere and PM-Scl, recombinant). • Single-antigen ELISAs available for detection of antibodies against cell nuclei Incubated ELISA Anti-SS-A, Anti-SS-B. and cytoplasm antigens: ssDNA, nucleosomes, dsDNA, histones, ribosomal P proteins, PM-Scl, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, centromere.

Order No. Formats EA ####-9601 G page 87

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Autoantibodies against Double-Stranded DNA (dsDNA)

Indirect Immunofluorescence Test: Crithidia luciliae • Detection of antibodies against dsDNA. • Indication: lupus erythematosus disseminatus. • Initial dilution: 1:10, conjugate class anti-human IgG, FITC-labelled. • Animal pathogenic haemoflagellates of Crithidia luciliae are used for the de- tection of autoantibodies against double-stranded, native DNA (dsDNA, nDNA) with indirect immunofluorescence. These protozoa possess a giant mitochon- drion containing dsDNA (kinetoplast) that, in general, does not show any of the other antigens present in the cell nuclei. Antibodies reacting with the kinetoplast are therefore only directed against dsDNA. EUROIMMUN Products for the

• Alongside the conventional CLIFT, which shows a particularly high disease Determination of Autoantibodies specificity, EUROIMMUN has developed an Anti-Crithidia luciliae sensitive IFT (order no. FA 1572-####-1), which is comparable in sensitivity to the Anti-dsDNA- NcX ELISA and the Farr assay. However, despite comparable sensitivities, the Crithidia luciliae: antibodies against dsDNA. assays identify different patients. To increase the serological hit rate different test systems are often combined.

Order No. Formats FA 1572-#### page 128

Microplate ELISA: Anti-dsDNA-NcX • Monospecific detection of antibodies against dsDNA. • Indication: lupus erythematosus disseminatus. • Serum dilution 1: 200, conjugate class anti-human IgG, POD-labelled. • Antibodies against dsDNA can be determined quantitatively in IU/ml. • 3-point calibration, quantitative. • Antigen: double-stranded DNA, complexed with nucleosomes (NcX). • Due to good sensitivity and specificity, the Anti-dsDNA-NcX ELISA stands out by high diagnostic efficiency. High concentrations of autoantibodies against dsDNA in the ELISA are considered to be a reliable marker for the diagnosis or prognosis of SLE. Individual changes in the dsDNA antibody concentration correlate with the activity of the disease and can be used for monitoring the development of the disease in SLE patients. In cases of immunosuppressive Incubated ELISA Anti-dsDNA-NcX. therapy or clinical remission dsDNA antibodies cannot be detected with the ELISA anymore.

Order No. Formats EA 1572-9601 G page 87

Anti-dsDNA RIA by Farr • Monospecific detection of antibodies against dsDNA. • ndication: lupus erythematosus disseminatus. • Use of undiluted samples. • Antigen: 125I-labelled dsDNA from plasmid DNA. • The Farr radioimmunoassay has always been of great importance. On the whole, it has the same specificity as the immunofluorescence test and the same sensitivity as the ELISA. Apparently, its well-known high diagnostic efficiency is based on the fact that only the fraction of the anti-dsDNA antibodies which is able to form bigger precipitating immune complexes with circulating DNA in liquid phase contributes to the measuring signal. The principle of the Farr test reflects, so to speak, the significant step in the pathomechanism of SLE: the formation of appropriate immune complexes, deposits of which build up in the RIA Anti-dsDNA. joints, kidneys, liver and other organs.

Order No. Formats RA 1571-0001 page 89

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Autoantibodies against CCP and Sa Determination of Autoantibodies

EUROIMMUN Products for the Microplate ELISA: Anti-CCP, Anti-Sa • Screening test for the specific determination of autoantibodies against cyclic citrullinated peptides (CCP) and citrullinated Sa. • Indication: rheumatoid arthritis (RA). • Serum dilution 1 : 100; conjugate class anti-human IgG, POD-labelled. • Antibodies against CCP and Sa can be determined quantitatively in RU/ml. Optional reference control for the determination of ratio values. • Antigen: synthetic cyclic citrullinated peptides (CCP, second generation), citrullinated Sa. Antigen Order No. CCP EA 1505-9601 G Incubated ELISA Anti-CCP, Anti-Sa. Sa EA 151a-4802 G

Order No. (Anti-CCP) Formats EA 1505-9601 G page 87

Antibodies against cyclic citrullinated peptides (CCP): An ELISA for specifi c diagnosis of rheumatoid arthritis

colourless chromogen stain H O H O N N POD peroxidase-labelled anti-human antibody Peptidylarginine- deiminase (PAD) POD Ca2+ NH NH human antibody against CCP + H2N NH2 O NH2 L-arginine L-citrulline synthetic CCP

The amino acid citrulline Principle of the anti-CCP ELISA Anti-CCP ELISA

Rheumatoid arthritis (RA) is one of the In recent years it has been shown that the calibration sera ensure reliable measure- most common autoimmune diseases, affect- rare amino acid citrulline, which is present in ment of antibody concentrations. The EURO- ing around 1% of the world population. It is fi laggrin, is a substantial component of the IMMUN Anti-CCP ELISA is a highly specifi c characterised by infl ammation of the syno- antigenic epitope. Enzyme immunoassays and sensitive sero logical test system for the vial membrane, which spreads symmetrical- which use synthetic citrullinated peptide diagnosis of RA. ly from the small to the large joints. Initial as the target antigen offer a useful alter- 2 Anti-CCP symptoms include painful swelling of Þ nger native to indirect immunofl uorescence . A Panel n joints with morning stiffness in the joints. direct comparison study demonstrated that positive Early diag nosis and immediate commence- the sensitivity can be increased from 49% Sensitivity RA 419 329 (78.5%) ment of suitable therapy is necessary to to 68% by using cyclic citrullinated peptide Asymptomatic blood keep the disease under control. instead of linear citrullinated peptide as an 400 2 (0.5%) donors ELISA substrate3. Antibodies against cyc li c The most commonly performed serological citrulli nated pep tides (CCP) are a new and Psoriatic arthritis280 test in suspected RA cases was until now the highly specifi c marker for RA. determination of rheumatoid factors (RF). Other arthritides 35 3 (8.6%) These are antibodies (predominantly of class An ti bodies against CCP are predominantly Systemic lupus 108 3 (2.8%) IgM) which react with gamma globulins and of class IgG and have a specifi city of 98% erythematosus occur in 60-80% of RA patients. RF are a sen- for RA. They are observed very early in the sitive but not very specifi c marker for RA, disease course and have a high predictive Sjögren‘s syndrome 106 2 (1.9%) since they also occur in healthy individuals value: patients with anti-CCP antibodies and in patients with various infections or develop signifi cantly more radiologically Scleroderma98 3 (3.1%) other autoimmune diseases (systemic lupus detectable joint damage than anti-CCP- Autoimmune 159 4 (2.5%) erythematosus, Sjögren’s syn drome, sclero- negative patients4. Antibodies against CCP thyroiditis derma and others). possess a much higher specifi city than RF Wegener‘ 25 1 (4.0%) (anti-CCP: 97%, RF: 62%) with the same sen- granulomatosis 40-60% of RA patients also exhibit auto- sitivity (anti-CCP: 79%, RF: 78%)5. They can Anti-parvovirus B19 126 3 (2.4%) anti bodies against epidermal fi l ag grin1 (RA be detected in early stages of the disease in positive

keratin, anti-pe ri nu clear fac tor) in their se- 79% of patients. Viral hepatides 54 0 rum. Fil ag grin is a protein of the epi dermis, which links keratin fi laments to one another. EUROIMMUN offers an innovative micro- Anti-HIV positive 5 0 Autoanti bodies against fi laggrin are detected plate ELISA for quantitative deter mina tion of by indirect immuno fl uores cence: the antigen autoantibodies against CCP. Diluted patient Tuberculosis100 substrate rat oesophagus shows staining of sera are incubated in wells coated with syn- the stratum corneum (RA keratin) on the thetic cyclic citrullinated peptides (second Specifi city RA 1154 21 (98.2%) luminal side; anti-perinuclear factors (APF) genera tion). Specifi c antibodies in the serum are apparent in the cyto plasmic inclusion bind to the immobi lised antigen and cause a 1) Nogueira et al., Ann. Rheum. Dis. 60: 882 (2001) 2) Schellekens et al., J. Clin. Invest. 101: 273-281 (1998) bodies of human epithelial cells of the oral photo metric colour reaction by means of an 3) Schellekens et al., Arthritis Rheum. 43: 155-163 (2000) 4) Kroot et al., Arthritis Rheum. 43: 1831-1835 (2000) mucosa. enzyme-coupled secondary antibody. Five 5) Vasishta, Am. Clin. Lab. 21: 34-36 (2002)

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Autoantibodies against Mitochondria (AMA)

Indirect Immunofluorescence Test: EUROPLUS™ Rat Kidney and M2-3E BIOCHIPs • Screening test for the detection of antibodies against mitochondria (AMA) in- cluding simultaneous confirmation of the subtype AMA M2. • Indication: primary biliary cirrhosis (PBC). • Initial dilution 1 : 100; polyvalent conjugate anti-human IgAGM, FITC-labelled. • Rat kidney is the standard substrate for detecting anti-mitochondrial antibodies. Nine AMA types (M1 to M9) can be differentiated. • The BIOCHIP coated with M2-3E permits monospecific confirmation of antibodies against the native pyruvate dehydrogenase complex and the EUROIMMUN Products for the

recombinant M2 fusion protein (BPO) in one single test procedure, thus a PBC Determination of Autoantibodies can be diagnosed serologically with confidence. • This BIOCHIP Mosaic™ can be supplemented as required using additional Rat kidney and M2-3E BIOCHIP: antibodies substrates, e.g. HEp-2 cells (ANA, nuclear dots), rat liver (liver-kidney micro- against mitochondria (AMA). somes, LKM) or rat stomach (ASMA).

Order No. Formats FA 1620-####-3 page 129

EUROASSAY: AMA Profile M2, M4, M9 • Differentiation of mitochondrial antibodies (AMA). • Indication: primary biliary cirrhosis (PBC). • Serum dilution 1 : 100; conjugate class anti-human IgGM, AP-labelled. • 3 relevant mitochondrial antibodies can be detected simultaneously and mono- specifically: antibodies against M2, M4, M9. • Native antigens: pyruvate dehydrogenase complex (M2), sulfite oxidase (M4), glycogen phosphorylase (M9). Anti- Associated diseases M2 Primary biliary cirrhosis (high titers), other chronic liver diseases M4 Primary biliary cirrhosis M9 Early phase of primary biliary cirrhosis Incubated EUROASSAY AMA Profile M2, M4, M9.

Order No. Formats DA 1620-####-1 O page 80

Microplate ELISA: Anti-M2-3E • Differentiation of mitochondrial antibodies (AMA). • Indication: primary biliary cirrhosis (PBC). • Serum dilution 1 : 100; conjugate class anti-human IgG, POD-labelled. • Antibodies against M2 can be determined quantitatively in RU/ml. • Antigen: native pyruvate dehydrogenase complex plus recombinant M2 fusion protein (BPO) containing the immunogenic domains of the E2 subunits of PDH, BCOADH and OGDH.

Incubated ELISA anti-M2-3E.

Order No. Formats EA 1622-9601 G page 88

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Autoantibodies against Liver Antigens Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: Liver Mosaic 8 • Screening and differentiation test for the detection of liver-specific antibodies, antibodies against mitochondria (AMA), antibodies against cell nuclei (ANA), antibodies against smooth muscles (ASMA), F-actin and other autoantibodies. • Indications: autoimmune hepatitis, primary biliary cirrhosis, rheumatic diseases. • Initial dilution 1 : 100; polyvalent conjugate anti-human IgAGM, FITC-labelled. • The BIOCHIP Mosaic™ consists of 6 substrates: human epithelial cells (HEp-2), primate liver, rat kidney, rat liver, rat stomach, VSM47. Thus, a broad spectrum of antigens is present, allowing not only targeted serological diagnoses, but also frequently yielding additional results with clinical relevance. • Antibodies against cell nuclei (ANA) can be particularly well demonstrated using HEp-2 cells and primate liver, and are identified according to their fluorescence patterns. However, they also stain the cell nuclei of the other tissues more or less intensely. Clinical significance: rheumatic diseases, primary biliary cirrhosis (antibodies against nuclear dots). • With primate liver, several liver-specific autoantibodies can be investigated e.g. antibodies against liver cell membrane (anti-LMA) and liver-specific protein (anti-LSP). Clinical significance: autoimmune hepatitis. • Antibodies against mitochondria (AMA) show a granular cytoplasmic fluo- rescence on all 6 substrates. With the standard substrate rat kidney, the proximal and distal tubule cells fluoresce equally. Clinical significance: primary biliary cirrhosis. • Autoantibodies against liver-kidney microsomes (anti-LKM) react with rat liver and rat kidney (see below). The other substrates are essentially negative. • In the case of autoantibodies against smooth muscles (ASMA), the tunica muscularis, the lamina muscularis mucosa as well as the interglandular con- tractile fibrils fluoresce on the rat stomach. ASMA directed against the target antigen F-actin furthermore react with the cytoskeleton of HEp-2 cells and the bile canaliculi of primate liver. The substrate VSM47 reacts very specifically, showing a filamentous, needle-like fluorescence. Clinical significance: autoimmune (lupoid) chronic active hepatitis. • The BIOCHIP Mosaic™ can be supplemented as required with additional sub- strates, e.g. Crithidia luciliae (antibodies against dsDNA), musculus iliopsoas (antibodies against skeletal muscles), heart (antibodies against striated muscles, antibodies against intercalated disks, AMA M7), different EUROPLUS™ sub- strates (AMA-M2-3E, Sp100, gp210, PML, SLA/LP, LC-1, LKM). HEp-2 cells: anti-nuclear dots. Primate liver: anti- LSP. Rat kidney: AMA. Rat liver: ANA. Rat stomach: ASMA. VSM47: Anti-actin.

Order No. Formats FA 1300-####-8 page 122

Indirect Immunofluorescence Test: BIOCHIP Mosaic™ Rat Liver/ Rat Kidney (Liver Mosaic 1) • Specific detection of antibodies against liver-kidney microsomes (anti-LKM). • Indications: autoimmune hepatitis, often associated with extrahepatic syndromes such as arthralgias, glomerulonephritis, vitiligo and chronic inflammatory bowel diseases. • Initial dilution 1 : 100; polyvalent conjugate anti-human IgAGM, FITC-labelled. • Autoantibodies against liver-kidney microsomes react with rat liver and generate a smooth staining in the cytoplasm of the hepatocytes. • In rat kidney, particularly in the cortex area, a fine granular fluorescence of the proximal tubules – recognizable by the luminal brush border – is visible. The distal tubules are negative. The fluorescence intensity of the liver cells is Rat liver and rat kidney: antibodies against liver- normally stronger than that of the proximal renal tubules. kidney microsomes (anti-LKM). • The differentiation between autoimmune hepatitis and virus-induced hepatitis can additionally be accomplished by investigating the appropriate viral parameters.

Order No. Formats FA 1300-####-1 page 122

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Autoantibodies against Liver Antigens

EUROLINE: Profile Autoimmune Liver Diseases AMA M2 • Differentiation of antibodies in autoimmune liver diseases. 3E (BPO) • Indications: autoimmune hepatitis, primary biliary cirrhosis, overlap syndromes. Sp100 • Serum dilution 1 : 100, conjugate class anti-human IgG, AP-labelled. PML • With the EUROLINE Profile Autoimmune Liver Diseases, nine autoantibodies can gp210 be determined: antibodies against AMA M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1, SLA/LP and Ro-52. LKM-1 • Test strips can be automatically incubated and evaluated using the systems LC-1 EUROBlotMaster und EUROLineScan (see page 27). SLA/LP • Further antigen combinations on page 79. Ro-52 EUROIMMUN Products for the Determination of Autoantibodies

control Anti- Associated Diseases M2, Sp100, PML, gp210 Primary biliary cirrhosis Incubated EUROLINE Profile Autoimmune Liver LKM-1, SLA/LP, LC-1 Autoimmune hepatitis Diseases. Ro-52 Autoimmune hepatitis, rheumatic diseases Order No. Formats DL 1300-1601-4 G page 80

EUROASSAY: Liver Profile (Anti-M2, -LKM-1, LC-1, -SLA/LP) • Determination of mitochondrial antibodies AMA M2, antibodies against liver- kidney microsomes type 1 (LKM-1), antibodies against liver cytosolic antigen type 1 (LC-1), as well as of antibodies against soluble liver antigen/liver-pancreas antigen (SLA/LP). • Indication: autoimmune liver diseases. • Serum dilution 1 : 100, conjugate class anti-human IgG, AP-labelled. • Antibodies against M2, LKM-1, LC-1 and SLA/LP can be detected simultaneously and monospecifically. • Antigens: pyruvate dehydrogenase complex (M2, native), cytochrome P450 IID6 (LKM-1, recombinant), formiminotransferase-cyclodeaminase (LC-1, recombi- nant) and soluble liver antigen/liver-pancreas antigen (SLA/LP, recombinant). Incubated EUROASSAY M2, LKM-1, LC-1, SLA/LP.

Order No. Formats DA 1300-1003-3 G page 79

Microplate ELISA: Anti-SLA/LP, Anti-LC-1, Anti-LKM-1 • Monospecific determination of antibodies against soluble liver antigen/liver- pancreas antigen (SLA/LP), cytosolic liver antigen type 1 (LC-1) and liver-kidney microsomes type 1 (LKM-1). • Indication: autoimmune hepatitis. • Serum dilution 1 : 100, conjugate class anti-human IgG, POD-labelled. • 3-point calibration, quantitative (exception: Anti-LC-1, semi-quantitative). • Identical incubation conditions and times: all tests can be combined without difficulty on one and the same microplate. • Recombinant antigens: soluble liver antigen/liver-pancreas antigen (SLA/LP), formiminotransferase-cyclodeaminase (LC-1) and cytochrome P450 IID6 (LKM-1). The corresponding human cDNA was expressed in E. coli (SLA/LP) or insect cells (LC-1, LKM-1). Incubated ELISA Anti-SLA/LP, Anti-LC-1, Anti-LKM-1.

Order No. (Anti-SLA/LP) Formats EA 1302-9601 G page 86

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Autoantibodies against Thyroid Gland Antigens / Antigen Detections Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: EUROPLUS™ Thyroid Gland (unfixed) and Thyroglobulin • Detection of antibodies against thyroid gland antigens. • Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis. • Initial dilution 1 : 10; conjugate class anti-human IgG, FITC-labelled. • Using unfixed thyroid tissue, two important thyroid-specific antibodies can be found: Autoantibodies against thyroid microsomes (MAb) give a granular staining in the cytoplasm of the follicle epithelium (target antigen: thyroid peroxidase, TPO). Autoantibodies against thyroglobulin (TAb) react with the colloid of all follicles of the thyroid tissue and cause a reticular fluorescence pattern. • With the thyroglobulin-coated BIOCHIP, autoantibodies against thyroglobulin Thyroid gland, unfixed and thyroglobulin (TG) can be confirmed monospecifically in one and the same test procedure. BIOCHIP: antibodies against thyroid microsomes • This BIOCHIP Mosaic™ can be supplemented as required with further substrates, and thyroglobulin. e.g. rat kidney, to achieve a differentiation of antibodies against thyroid microso- mes from mitochondrial antibodies (AMA). For a serological diagnosis of auto- immune polyendocrinopathies, BIOC Order No. Formats FA 1010-####-3 page 116

Radioimmunoassays (RIA/IRMA): Thyroid Specific Autoantibodies, Antigens and Hormones • Monospecific detection of autoantibodies against thyroglobulin (TG), thyroid peroxidase (TPO) and thyrotropin receptor (TSH-R). • Specific detection of the thyroid antigen thyrotropin and the hormones free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), calcitonin. • Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis, medullary thyroid carcinoma, thyroidal C-cell hyperplasia, therapy controls in hyper- and hypothyrosis. • Serum dilutions: 1:50 for anti-TG and anti-TPO (magnetic), 1:20 for anti-TG and anti-TPO (precipitation), undiluted for all remaining test kits. • 5-point to 8-point calibration (quantitative). RIA for thyroid diagnostics. Analyte Order No. Analyte Order No. Anti-TPO RA 1012-####-# FT3 RD 1016-10001 Anti-TG RA 1013-10001-# FT4 RD 1017-10001 TRAb RA 1015-10001 TSH RD 1018-10001 Order No. (Anti-TPO) Formats Thyrotropin RD 1013-10001 Calcitonin RD 1019-10001 RA 1012-####-# page 89

Microplate ELISA: Anti-Thyroglobulin, Anti-Thyroid Peroxidase, Anti-TSH receptor • Monospecific determination of antibodies against thyroglobulin (TG), thyroid peroxidase (TPO), and thyrotropin receptor (TSH-R). • Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis. • Serum dilution 1 : 200 (exception: anti-TSH-R undiluted); conjugate class anti- human IgG, POD-labelled (anti-TSH-R: avidin-labelled). • 3-point calibration (exception: anti-TSH-R, 5-point calibration). • The quantification is carried out according to international reference preparations (anti-TG: NIBSC 65/93; anti-TPO: NIBSC 66/387; anti-TSH-R: NIBSC 90/672). • Thyroglobulin/TSH-R: native antigen; thyroid peroxidase: recombinant antigen. Incubated ELISA Anti-Thyroid antigens. Antigen Order No. Thyroid peroxidase EA 1012-9601 G Thyroglobulin EA 1013-9601 G TSH receptor EA 1015-9601 G Order No. (Anti-TPO) Formats TSH receptor (Fast-ELISA) EA 1015-9601-1 G EA 1012-9601 G page 86

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Autoantibodies against Antigens of the Skin

Indirect Immunofluorescence test: Dermatology Mosaic 9 • Screening and differentiation test for detection of skin-specific antibodies. • Indication: autoimmune bullous dermatoses. • Initial dilution 1 : 10; conjugate class anti-human IgG, FITC-labelled. • The BIOCHIP Mosaic consists of 6 substrates:primate oesophagus,desmoglein 1- expressing cells, desmoglein 3-expressing cells, BP230-expressing cells (whole length), BP230-expressing cells (gC) and BP180 (EUROPLUS). Thus a comprehensive antigen spectrum is available in a single analysis, allowing targeted serological diagnosis. • Autoantibodies against intercellular target structures (prickle cell desmosomes) EUROIMMUN Products for the

can be reliably detected using tissue sections of oesophagus and tongue, Determination of Autoantibodies although with this combination it is difficult to distinguish between desmoglein 1 and desmoglein 3. When specific transfected cells are employed in addition, a targeted diagnosis in a single test run is possible. • Antibodies against prickle cell desmosomes Antibodies against prickle cell desmosomes react with surface antigens of keratinocytes. Tissue sections of oesophagus and tongue show a granular fluorescence in the intercellular matter in the whole stratum spinosum. • When autoantibodies against BP180 or BP230 are present, the epidermal basement membrane in the oesophagus or tongue is visible as a fine linear colouring between the stratum basale and the connective tissue. These antibodies can be differentiated by means of BP180-NC16A-4X coated BIOCHIPS and cells transfected with BP230 (whole length or globular C-terminal domain (gC), respectively. • This BIOCHIP Mosaic can be customised with further substrates if required, e.g. tongue (antibodies against prickle cell desmosomes, epidermal basement membrane), bladder (antibodies against plakins), salt split skin (antibodies against epidermal basement membrane). Substrate Order No. Desmoglein 1 (transfected / non-transfected cells) FA 1495-####-50 Desmoglein 3 (transfected / non-transfected cells) FA 1496-####-50 Oesophagus FA 1501-#### Oesophagus / Tongue FA 1501-####-1 Tongue FA 1502-#### Oesophagus: ab against epid. basal membrane (top left). Desmoglein 1 + 3 (middle left, bottom Bladder mucosa FA 1507-#### left). BP230 gC (top right). BP230 whole length (middle right). BP180 (NC16A-4X) (bottom right). Salt split skin FA 150b-#### Order No. Formats FA 1501-####-9 G page 125

Microplate ELISA: Anti-Desmoglein 1, Anti-Desmoglein 3, Anti- BP180-NC16A-4X, Anti-BP230-CF • Monospecific detection of antibodies against desmoglein 1, desmoglein 3, BP180 und BP230. • Indication: autoimmune bullous dermatoses. • Serum dilution 1 : 100; conjugate class anti-human IgG, POD-labelled. • 3-point calibration, quantitative. • Identical incubation conditions and times: all tests can be combined on one microplate. • Recombinant antigens: extracellular domain of desmoglein 1 or 3, tetramer of NC16A domain of BP180 protein, C-terminal segment of BP230 protein. The corresponding human cDNA is produced in E. coli (BP180-NC16A-4X, BP230-CF) or in mammalian cells (desmoglein 1, desmoglein 3).

Incubated ELISA Anti-Desmoglein 1 and 3, Anti- BP180-NC16A-4X, Anti-BP230-CF

Order No. (Anti-Dsg-1) Formats EA 1495-4801 G page 87

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Autoantibodies against Neuronal Antigens Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: BIOCHIP Mosaic™ Cerebellum/ Peripheral Nerves/Intestinal Tissue • Screening test for the detection of antibodies against neuronal antigens. • Indications: neurological diseases. • Initial dilution 1 : 10; conjugate class anti-human IgAGM, FITC-labelled. • Primate cerebellum and primate nerves are the standard substrates for the determination of various neuronal antibodies. The parallel use of primate intestine permits the reliable differentiation from other autoantibodies (e.g. ANA) and makes it possible to distinguish between anti-Ri and anti-Hu. • Antibodies against grey matter react intensively with the stratum granulosum and in a weaker form with the stratum moleculare of the cerebellum. Target antigen: glutamic acid decarboxylase (GAD). Clinical significance: stiff person syndrome, diabetes mellitus type I. • Antibodies against Yo stain exclusively the cytoplasm of the Purkinje cells in the cerebellum. Clinical significance: paraneoplastic neurological syndromes (PNS), indication of a malignoma. • In the case of antibodies against Hu and Ri all neurone nuclei in the grey matter show a granular fluorescence. Hu antibodies react in the intestine with cell nuclei of the plexus myentericus, whereas Ri antibodies do not. Clinical significance: paraneoplastic neurological syndromes (PNS), indication of a malignoma. • The white matter of the cerebellum is stained by antibodies against myelin, which present as hyaline cylinders in tissue sections of peripheral nerves. A “droplike“ ring-shaped fluorescence is observed in cross sections of nerves. • The fluorescence of the Virchow-Robin space (cerebellum, optic nerve) and the pia is caused by autoantibodies developed in neuromyelitis optica (NMO-IgG). • Antibodies against myelin-associated glycoprotein (MAG), on the other hand, show a streaky fluorescence pattern on nerve tissue and a mostly fine-granular ring-shaped fluorescence on cross sections of peripheral nerves. Clinical significance: paraproteinaemic neuropathy. • The BIOCHIP Mosaic™ can be supplemented as required with further substrates, e.g. cerebrum (antibodies against astrocytes), optic nerve, primate liver plus HEp-2 cells (to rule out ANA), Crithidia luciliae (anti-dsDNA), primate stomach (parietal cell antibodies), Borrelia (neuroborreliosis-associated). Aquaporin- 4(AQP4) transfected HEK cells allow a monospecific antibody determination in suspected cases of neuromyelitis optica (NMO). Cerebellum: antibodies against GAD and Yo (top), against Hu and Ri (middle). Peripheral nerves: antibodies against myelin and MAG (bottom).

Order No. Formats FA 1111-####-1 page 117

EUROLINE: Neuronal Antigens Profile 2 amphiphysin • Differentiation of antibodies against neuronal antigens. CV2.1* • Indication: paraneoplastic neurologic syndromes (PNS). PNMA2 (Ma2/Ta) • Serum dilution 1 : 100; conjugate class anti-human IgG, AP-labelled. Ri • With the EUROLINE Neuronal Antigens Profile 2, six autoantibodies can be Yo determined: antibodies against amphiphysin, CV2.1*, PNMA2 (Ma2/Ta), Ri, Yo and Hu. Hu • Test strips can be automatically incubated and evaluated using the systems EUROBlotMaster und EUROLineScan (see page 27). • Additionally, EUROIMMUN offers a Westernblot for the detection of antibodies against neuronal antigens: DW 1111-1601 G. control *) CV2 partial protein, which only contains the N-terminally localised epitopes of the antigen.

Incubated EUROLINE Neuronal Antigens Profile 2.

Order No. Formats DL 1111-1601-2 G page 80

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Autoantibodies against Neuronal Antigens

Indirect Immunofluorecence test: BIOCHIP Mosaic™ Hippocampus/ Cerebellum/NMDA Receptor • Screening test for detection of antibodies against glutamate receptors (type NMDA, anti-N-methyl-D-aspartate receptor) und neuropil. • Indication: NMDAR encephalitis. • Initial dilution 1 : 10; conjugate class anti-human IgG, FITC-labelled. • Immunohistochemistry with tissue sections of rat hippocampus and rat cerebellum allows identification of antibodies against glutamate receptors (type NMDA) and other antibodies (e.g. VGKC and AMPA receptors). The parallel use of recombinant HEK293 cells enables sensitive and monospecific detection of EUROIMMUN Products for the

anti-glutamate receptor (type NMDA) antibodies and their differentiation from Determination of Autoantibodies other neuropil antibodies in a simple and efficient analysis. • Antibodies against glutamate receptors (type NMDA) stain the neuropil of the molecular layer of the hippocampus as well as the granular layer of the cerebellum. They show a flat, smooth to fine-granular fluorescence in the cytoplasm of the transfected HEK293 cells. Clinical significance: Anti-NMDA receptor encephalitis. • If the monospecific detection of antibodies against glutamate receptors of type NMDA is negative, neuropil fluorescence can indicate the presence of other antibodies associated with limbic encephalitis (e.g. anti-VGKC antibodies, anti- AMPA receptor antibodies).

Antibodies against glutamate receptor (type NMDA): rat hippocampus (top left), rat cerebellum (bottom left), untransfected cells (top right), transfected cells (bottom right).

Order No. Formats FA 111m-####-3 G page 118

EUROLINE-WB: Anti-Neuronal Antigens • Determination of human autoantibodies against neuronal antigens. • Indication: paraneoplastic neurological syndromes (PNS). • Serum dilution 1 : 51; conjugate class anti-human IgG, AP-labelled. Ri • EUROLINE-WB is a combination of westernblot and line blot techniques. Yo Ri Proteins of a primate cerebellum extract are electrophoretically separated according to molecular mass and transferred onto a nitrocellulose membrane Hu (westernblot). A membrane chip coated with highly purified recombinant Hu, Yo recombinant Ri and recombinant Yo is subsequently applied to the westernblot strip. • Test strips can be automatically incubated using the system EUROBlotMaster (Seite 27). rec. Ri rec. Yo rec. Hu

Control Incubated Anti-Neuronal Antigens EUROLINE-WB.

Order No. Formats DW 1111-####-2 G page 83

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Autoantibodies against Islet Cell Antigens Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: Primate Pancreas • Detection of antibodies against islet cells. • Indications: Differentiation between a late manifestation of diabetes type 1 (latent autoimmune diabetes in adulthood, LADA) and diabetes type 2. • For a reliable determination of antibodies against islet cells an extended incubation time of 18 hours for the patient serum must be observed. The incubation time may be reduced to 2 hours but this will lead to a decrease in the sensitivity of the antibody detection test. • Standardised control with JDF units available (order no. CA 1021-0101-1). • With indirect immunofluorescence autoantibodies against pancreas islets (ICA) can be detected in 80% of patients with new-onset diabetes type 1. Two target antigens of ICA have been identified so far: the enzymes glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA2). Primate pancreas: antibodies against islet cells. • This BIOCHIP may be supplemented with further substrates, e. g. primate cerebellum for the detection of antibodies against GAD. • The microscopic evaluation can be significantly simplified by using small BIOCHIPs (1 x 1 mm). The BIOCHIPs appear almost completely in the field of view and facilitate finding the islet cells, thus rendering a time-consuming Order No. Formats search unnecessary, especially in negative samples. FA 1020-#### page 116

Microplate ELISA: Anti-GAD, Anti-IA2, Anti-GAD/IA2 Pool • Monospecific detection of antibodies against glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2) or bispecific detection of both antibodies in a single reagent well. • Indications: early diagnosis of diabetes mellitus type 1, risk prediction in first grade relatives, prognosis of the clinical progression of diabetes type 1 for prediction of insulin dependence, differential diagnosis in gestational diabetes, differentiation between a late manifestation of diabetes type 1 (latent autoimmune diabetes in adulthood, LADA) and diabetes type 2. • Use of undiluted samples. Similar incubation conditions and times. Manual or automated test performance. • Multipoint calibration. The quantitation is based on an international reference preparation (NIBSC 97/550). Incubated ELISA anti-GAD. • GAD and IA2: human, recombinant antigens. Antigen Order no. Glutamic acid decarboxylase (GAD)EA 1022-9601 G Order No. (Anti-GAD) Formats Tyrosine phosphatase (IA2) EA 1023-9601 G EA 1022-9601 G page 86 GAD/IA2 Pool EA 1022-9601-1 G

RIA: Anti-GAD, Anti-IA2, Anti-Insulin • Monospecific detection of antibodies against glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2) and insulin. • Indications: Early diagnosis of diabetes mellitus type 1, risk prediction in first grade relatives, prognosis of the clinical progression of diabetes type 1 for prediction of insulin dependence, differential diagnosis in gestational diabetes, differentiation between a late manifestation of diabetes type 1 (latent autoimmune diabetes in adulthood, LADA) and diabetes type 2. • Use of undiluted samples. Similar incubation conditions and times. Manual or automated test performance. • Test kit formats for 50 or 100 determinations. • GAD and IA2: human, recombinant, 125I-labelled antigens, insulin: human, synthetic, 125I-labelled antigen. RIA Anti-IA2. Antigen Order no. Glutamat-Decarboxylase (GAD) RA 1022-#### Tyrosin-Phosphatase (IA2) RA 1023-#### Order No. (Anti-IA2) Formats Insulin RA 1024-#### RA 1023-#### page 89

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Autoantibodies against Parietal Cells (PCA)

Indirect Immunfluorescence Test: Primate Stomach with Urea Pretreatment • Screening test for detection of antibodies against parietal cells. • Indications: forms of chronic atrophic gastritis, pernicious anemia, funicular myelosis, various autoimmune endocrinopathies such as Basedow’s and Addison’s diseases. • Initial dilution 1 : 10; polyvalent conjugate anti-human IgAGM, FITC-labelled. • Primate stomach is the standard substrate for detection of parietal cell antibodies. For titration, stomach tissue from rat or mouse is sufficient. • With positive results the parietal cells show a course granular to clumpy EUROIMMUN Products for the

fluorescence, and the surrounding areas are usually dark. Determination of Autoantibodies • Parietal cell antibodies (PCA) are often mixed up with antibodies against mitochondria (AMA) in microscopic analysis. The latter give an even fine granular fluorescence of the parietal cell cytoplasm, with the surrounding region showing a (weaker) reaction. Primate stomach: antibodies against parietal • For reliable differentiation of both types of antibody, a 30-minute pretreatment cells. With urea-pretreatment (top) and without of the tissue sections with urea-glycine buffer (order no. ZF 1140-0101, see page urea-pretreatment (bottom). 151) is recommended. • The cytomplasmic fluorescence of parietal cells resulting from PCA occurs with the same intensity with or without urea pretreatment. The typical pattern of mitochondrial antibodies is almost completely supressed by urea pretreatment, greatly facilitating PCA diagnostics. • In some AMA-positive samples it is possible to detect PCA that are obscured by the AMA pattern in conventional tissue sections. • The urea-pretreated tissue shows a significantly darker background, enabling specific fluorescence to be more easily and reliable identified. • This BIOCHIP can be supplemented with additional substrates, for example, thyroid (thyroid peroxidase, thyroglobulin), pancreas (pancreas islets), adrenal gland (adrenal cortex), ovary (ovary antigens), testis (Leydig cells), and intrinsic factor.

Primate stomach: antibodies against mitochon- dria. With urea-pretreatment (top) and without urea-pretreatment (bottom).

Order No. Formats FA 1360-#### G page 122

Microplate ELISA: Anti-Parietal Cells • Monospecific detection of antibodies against parietal cells (PCA). • Indications: forms of chronic atrophic gastritis, pernicious anemia, funicular myelosis, various autoimmune endocrinopathies such as Basedow’s and Addison’s diseases • Serum dilution 1 : 200; conjugate class anti-human IgG, POD-labelled. • 3-point calibration, quantitative. • Native antigen: H+/K+-ATPase, purified by affinity chromatography.

Incubated ELISA Anti-Parietal Cells.

Order No. Formats EA 1361-9601 G page 86

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Autoantibodies against Granulocyte Cytoplasm (cANCA/pANCA) Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: EUROPLUS™ Granulocyte Mosaic 23 • Screening test for the detection of antibodies against granulocyte cytoplasm (ANCA). • Indications: Wegener’s granulomatosis, various forms of glomerulonephritis, primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease. • Initial dilution: serum 1 : 10; conjugate anti-human IgG, FITC-labelled. • Using ethanol-fixed granulocytes, antibodies against granulocyte cytoplasm can be detected. In this case, two fluorescence patterns have to be differentiated: a granular fluorescence which is distributed evenly over the entire cytoplasm, leaving the cell nuclei free (cytoplasmic type, cANCA) or a smooth fluorescence wrapped ribbon-like around the cell nuclei (perinuclear type, pANCA). • Antibodies against all relevant granulocyte antigens as well as against further, as yet unknown antigens are detected simultaneously: Pattern Target antigen Associated diseases cANCA Proteinase 3 Wegener’s granulomatosis pANCA Myeloperoxidase Microscopic arteritis, Churg-Strauss syndrome, polyarteritis nodosa pANCA Elastase Ulcerative colitis, Crohn’s disease, primary sclero- sing cholangitis, systemic lupus erythematosus pANCA Cathepsin G Ulcerative colitis, primary sclerosing cholangitis, Crohn’s disease pANCA Lysozyme Ulcerative colitis, primary sclerosing cholangitis, Crohn’s disease pANCA Lactoferrin Ulcerative colitis, primary sclerosing cholangitis, Crohn’s disease, systemic lupus erythematosus, rheumatoid arthritis cANCA BPI Primary sclerosing cholangitis, ulcerative colitis, or pANCA Crohn’s disease pANCA unknown Ulcerative colitis, Crohn’s disease • The primate liver enables one to differentiate between pANCA and anti-nuclear antibodies (ANA) which can easily be confused when using ethanol-fixed granu- locytes: In the case of a positive ANA result all nuclei of the hepatocytes fluoresce, whereas in the case of pANCA (as well as cANCA) only the EUROPLUS™ Granulocyte Mosaic 23 (granuloc. granulocytes in the sinusoids of primate liver fluoresce. (EOH), granuloc. (HCHO), PR3, MPO, HEp-2, pri- • The EUROPLUS substrates PR3 and MPO as monospecific tests can confirm mate liver): pattern pANCA, formalin-resistant. results from conventional granulocyte screening tests. Recombinant GBM EUROPLUS substrate also provides additional reliability for diagnosis. When Order No. Formats fluorescence patters are unclear (e.g. unspecific fluorescence caused by other FA 1201-####-23 page 120 cytoplasmic antibodies) these substrates facilitate evaluation.

Microplate ELISA: ANCA Profile • Differentiation of antibodies against granulocyte cytoplasm (ANCA). • Indications: Wegener’s granulomatosis, various forms of glomerulonephritis, primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease. • Serum dilution 1 : 100; conjugate class anti-human IgG, POD-labelled. • 6 relevant anti-granulocyte antibodies can be detected simultaneously and monospecifically: autoantibodies against proteinase 3, lactoferrin, myelo- peroxidase, elastase, cathepsin G, BPI. • 1-point calibration, semi-quantitative. Calibrator pool and serum sample on the same microplate strip. • Native antigens, purified by affinity chromatography. • Available individual ELISA (3-point calibration, quantitative): Incubated ELISA ANCA Profile (antigens: pro- teinase 3, lactoferrin, myeloperoxidase, elastase, Antigen Order No. cathepsin G, BPI. Proteinase 3 (Capture ELISA) EA 1201-9601-1 G Proteinase 3 (PR3-hn-hr: native/recombinant) EA 1201-9601-2 G Myeloperoxidase EA 1211-9601 G Order No. Formats EA 1200-1208-1 G page 86

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Cost-effective Strategy for the Detection of Autoantibodies against Granulocyte Cytoplasm (ANCA)

Screening test indirect immunofluorescence: BIOCHIP sextet granulocytes (EOH), granulocytes (HCHO), EUROPLUSTM microdots PR3, EUROPLUSTM microdots MPO, human epithelial cells (HEp-2), and primate liver

Perinuclear fluorescence of Fluorescence of all cell nuclei Fluorescence of all cell nuclei Cytoplasmic fluorescence granulocytes (A, F) (A, E, F) (A, E, F), granuloc. accent. (F) of granulocytes (A, B, F)

A F

Granulocytes Primate (EOH-fixed) liver

B E EUROIMMUN Products for the

Granulocytes HEp-2 Determination of Autoantibodies (HCHO-fixed) cells

C D EUROPLUSTM EUROPLUSTM PR3 MPO microdots microdots

pANCA only ANA ANA and pANCA cANCA MPA 42-70 % CU 67 % WG 80-90 % CSS 18-60 % MC 7 % MPA 10-15 % SLE 9-25 % PSC 87 % CSS 10-20 % RA 3-25 % PAN < 9 %

At B cytoplasmic At B no cytoplasmic Cytoplasmic fluorescence Nuclei of granuloc. brighter than ANCA reaction at A, fluorescence fluorescence of granulocytes (B) nuclei of hepatocytes (F), B neg. ANA reaction at E & F

pANCA, formalin-resistant pANCA, formalin-sensitive pANCA, formalin-res. & ANA pANCA, formalin-sens. & ANA pANCA, formalin-sens.? & ANA MPA 42-70 %

ELISA: anti-MPO ELISA: ANCA Profile Qualified ANA diagnostics: screening test using ELISA: anti-PR3-hn-hr / ANCA Profile (BPI) HEp-2 cells/primate liver (E, F), differentiation AAb against AAb against PR3, MPO, using ELISA, EUROASSAY, EUROLINE, Westernblot AAb against AAb against MPO elastase, cathepsin G, PR3-hn-hr BPI BPI, lactoferrin AAb against dsDNA, ssDNA, nucleosomes, histones, nuclear membrane, nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Ku, cyclin I (PCNA), mitosin WG 80-90 % WG 5 % WG 5 % (BPI) (CENP-F, cyclin II), nuclear dots, centromeres MPA 53 % (MPO) (CENP B), spindle fibres, midbody, centrioles, MPA 53 % MPA 3 % (LF) Scl-70, PM-Scl, fibrillarin, RNA polymerase I, RA, vasculitides 45 % (LF) NOR, ribosomal P-proteins, Jo-1, PL-7, PL-12, See EUROIMMUN poster: "Strategy for Determination SLE 6 % (EL) Mi-2, mitochondria (AMA), lysosomes, Golgi of Autoantibodies against Cell Nuclei (ANA) apparatus, vimentin, tropomyosin, actin. and Cytoplasm Components"

The highest diagnostic sensitivity in the determination of autoantibodies against neutrophil granulocytes (ANCA) is achieved by using indirect immunofluorescence and assays with defined target antigens (particularly PR3 and MPO) simultaneously at the start. However, under the pressure of cost optimisation, an immunofluo- rescence test may be performed on its own and then followed up by specific ELISA tests only if the result is positive. Ethanol-fixed human granulocytes are the standard substrate for indirect immunofluorescence. With this substrate two relevant fluorescence patterns can be differentiated: the cytoplasmic type (cANCA) associated with Wegener’s granulomatosis and the perinuclear type (pANCA), which indicates a range of various diseases. The differentiation of pANCA from antibodies against cell nuclei (ANA) is often difficult. Therefore, HEp-2 cells (possibly with sedimented granulocytes) or primate liver are used as an additional substrate. If ANA and pANCA occur together, the granulocytes show a much brighter fluorescence than the cell nuclei. Thanks to EUROIMMUN BIOCHIPs it is not necessary to incubate human epithelial cells on a second slide in parallel for the exclusion of cell nucleus antibodies, since all substrates are present in one and the same test field. A fourth BIOCHIP with formalin-fixed human granulocytes detects a large proportion of the diagnostically relevant antibodies against myeloperoxidase, whereas other pANCA (which are particularly important in gastroenterology) and almost all antibodies against cell nuclei (whose differentiation is a separate chapter in autoantibody diagnostics) are generally completely suppressed. The EUROPLUSTM substrates PR3 and MPO help to confirm diagnosis and allow a quick and reliable interpretation of results even in problematic cases.

ANA: anti-nuclear antibodies BPI: bactericidal permeability increasing protein cANCA: anti-neutrophil cytoplasmic antibodies, cytoplasmic type CD: Crohn‘s disease CSS: Churg-Strauss syndrome EL: elasta- se EOH: ethanol HCHO: formalin HEp-2: human epithelial cells IFT: immunofluorescence test LF: lactoferrin MPA: microscopic polyangiitis MPO: myeloperoxidase PAN: polyarteritis nodosa pANCA: anti-neutro- phil cytoplasmic antibodies, perinuclear type PR3: proteinase 3 PSC: primary sclerosing cholangitis RA: rheumatoid arthritis SLE: systemic lupus erythematosus UC: ulcerative colitis WG: Wegener‘s granulomatosis —47—

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Antibodies against Endomysium and Gliadin Determination of Autoantibodies

EUROIMMUN Products for the Indirect Immunofluorescence Test: EUROPLUS™ Primate Liver and Gliadin (GAF-3X) BIOCHIPs • Detection of antibodies against endomysium and gliadin. • Indications: gluten-sensitive enteropathy (celiac disease, non-tropical sprue), Duhring’s herpetiform dermatitis. • Initial dilution 1 : 10; conjugate class anti-human IgA or IgG, FITC-labelled. • Autoantibodies against endomysium react with many types of tissue, e.g. primate oesophagus. The most suitable substrate, however, is primate liver: in the case of a positive sample, filamentous linings of the intralobular sinusoids react. • With the gliadin (GAF-3X)-coated BIOCHIP, antibodies against gliadin can be analyzed in one and the same test procedure. Primate liver and gliadin (GAF-3X) BIOCHIP: anti- • Both anti-endomysium antibodies and antibodies against gliadin (class IgA) are bodies against endomysium and gliadin. reliable serological markers for an active gluten-sensitive enteropathy. Therefore, their determination can in many cases replace endoscopy and biopsy.

Order No. Formats FA 1914-####-1 A or G page 132

Microplate ELISA: Anti-Gliadin (GAF-3X) • Monospecific detection of antibodies against gliadin. • Indications: gluten-sensitive enteropathy (celiac disease, non-tropical sprue), Duhring’s herpetiform dermatitis. • Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled. • 3-point calibration. Identical incubation conditions and times: the investigation of IgA and IgG antibodies can be combined without difficulty on one and the same microplate. • Antigen: Gliadin-analogue fusion peptide (GAF-3X). • The quantitative determination of antibodies against gliadin is very suitable for monitoring the progress of the disease, compliance with a gluten-free diet, or a gluten tolerance test. Incubated ELISA Anti-Gliadin (GAF-3X).

Order No. Formats EV 3011-9601 A or G page 95

Microplate ELISA: Anti-Tissue Transglutaminase (Endomysium) • Monospecific detection of antibodies against tissue transglutaminase. • Indications: gluten-sensitive enteropathy (celiac disease, non-tropical sprue), Duhring’s herpetiform dermatitis. • Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled. • 3-point calibration, quantitative. • Antigen: recombinant, expression with the baculovirus vector in insect cells.

Incubated ELISA Anti-Tissue Transglutaminase (Endomysium).

Order No. Formats EA 1910-9601 A or G page 88

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EUROIMMUN PRODUCTS FOR INFECTIOUS SEROLOGY

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Antibodies against Borrelia

Indirect Immunofluorescence Test: EUROPLUS™ Anti-Borrelia afzelii, Borrelia burgdorferi, VlsE and OspC Antigen • Sensitive screening test for the detection of anti-Borrelia antibodies. • Indications: erythema chronicum migrans, lymphadenosis cutis benigna, lym-

EUROIMMUN Products for phocytic meningoradiculitis, carditis, arthritis, acrodermatitis chronica atro- phicans, neuroborreliosis. Infectious Serology • Initial dilution 1 : 10 (IgM), 1 : 100 (IgG). • If antibodies against Borrelia afzelii or Borrelia burgdorferi are present, a distinct fluorescence of the bacteria in the smear is obtained. • With the VlsE or OspC coated BIOCHIPs antibodies against the highly specific and highly sensitive marker antigens VlsE (IgG) or OspC (IgM) can be determined monospecifically in one and the same test procedure. If these Antibodies against Borrelia afzelii, VlsE (top), antigens fluoresce the antibody result is positive even if the bacteria smears Borrelia burgdorferi and OspC (bottom). show a negative reaction. Thus, the BIOCHIP Mosaic helps to increase specificity and sensitivity in Borrelia diagnostics. • The BIOCHIP can be supplemented as required using further substrates, e.g. Borrelia burgdorferi sensu stricto (strains CH or USA) and TBE virus infected cells. Order No. Formats FI 2136-####-1 G or M page 136

Microplate ELISA: Anti-Borrelia plus VlsE • Sensitive screening test for the detection of anti-Borrelia antibodies. • Indications: erythema chronicum migrans, lymphadenosis cutis benigna, lym- phocytic meningoradiculitis, carditis, arthritis, acrodermatitis chronica atro- phicans, neuroborreliosis. • Serum dilution 1 : 100; conjugate class anti-IgG, anti-IgM or anti-IgAGM (VlsE: - IgG only), POD-labelled. • 3-point calibration (IgG and IgM). Identical incubation conditions and times: all tests can be combined without difficulty on one and the same microplate. • Antigens: extract of Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii (whole antigen) / recombinant VlsE from Borrelia burgdorferi sensu stricto. VlsE (variable major protein-like sequence, expressed) is a newly characterized surface protein of Borrelia which is expressed exclusively in vivo Incubated ELISA Anti-Borrelia plus VlsE. and which contains conserved and highly immunogenic epitopes. • IgM test kit (Anti-Borrelia) includes IgG/RF absorbent in sample buffer for IgG absorption in preparation for the determination of specific IgM class antibodies.

Order No. Formats EI 2132-9601 G or M page 91

Microplate ELISA: Anti-Borrelia plus VlsE, Antibody Determination in Serum and Cerebrospinal Fluid for Detection of Intrathecal Synthesis of Specific Antibodies against Borrelia • Antibody determination in serum and cerebrospinal fluid (CSF). • Indication: Neuroborreliosis. • CSF dilution 1 : 2, serum dilution 1 : 404; conjugate class anti-IgG, POD-labelled. • 4-point calibration, quantitative. • Microplate ELISA for the detection of Borrelia antibodies of class IgM in serum and CSF are also available.

Table-based evaluation of the CSQrel.

Order No. Formats EI 2132-9601 L G page 91

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Antibodies against Borrelia

Anti-Borrelia EUROLINE-RN-AT VlsE B. burgd. VlsE B. afzelii p41 B. afzelii VlsE B. burgdorferi p39 B. afzelii • Specific confirmatory test for the detection of antibodies against Borrelia. VlsE B. garinii OspC B. afzelii Lipid B. afzelii • Indications: erythema chronicum migrans, lymphadenosis cutis benigna, lym- OspC B. burgd. Lipid B. burgdorferi phocytic meningoradiculitis, carditis, arthritis, acrodermatitis chronica atro- OspC B. garinii phicans, neuroborreliosis. p83 B. afzelii p41 B. garinii • The Anti-Borrelia EUROLINE is coated with both native and recombinant p39 B. garinii proteins and provides a unique mixture of Borrelia specific antigens: The OspC B. garinii classical antigens OspC, p83 and p39, which show the highest specificity in their p58 native form, were accurately cut from a Westernblot and applied onto the p21 membrane of the line blot. Five new, recombinant designer antigens (p18, p19, p20 p19 p20, p21, p58) having a very high specificity (IgG) were identified using p18 bioinformatic analysis of the Borrelia genome. For the first time, lipids which have been proven to be immunoreactive and were extracted from the Borrelia IgM IgG membranes, three native OspC antigens (IgM) from B. afzelii, B. burgdorferi Control band Control band Infectious Serology

and B. garinii and three different VlsE antigens (IgG) from B. afzelii, B. EUROIMMUN Products for burgdorferi and B. garinii are available on the line blot. • The serological hit rate is increased by 10% by using three OspC variants in the Incubated Anti-Borrelia EUROLINE-RN-AT . IgM test. • Serum dilution 1 : 50; conjugate class anti-IgG or anti-IgM, AP-labelled. Order No. Formats DN 2131-3201 G or M page 81

EUROLINE-WB: Anti-Borrelia (Whole Antigen plus VlsE) VlsE • Specific confirmatory test for the detection of antibodies against Borrelia. p 83 • EUROLINE-WB is a combination of westernblot and line blot techniques. An SDS extract of a Borrelia afzelii strain is electrophoretically separated according to molecular mass and transferred onto a nitrocellulose membrane. A p 41, Flag. membrane chip coated with highly purified recombinant VlsE-Antigen is then p 39, Bmp A added to the westernblot strips. p 31, Osp A • By additionally determining antibodies against VlsE the serological hit rate can p 30 be increased by 20% compared to whole extract Westernblots and by 30% compared to recombinant antigen Westernblots. Of all recombinant antigens, p 25, Osp C VlsE possesses the highest sensitivity for the detection of a Borrelia infection. p 21 Over 85% of IgG-positive sera could be identified at a glance by assessing the p 19 VlsE band. VlsE allows detection of antibodies against all Borrelia species, and p 17 the risk of a false negative reaction due to species differences is ten times lower.

• Serum dilution 1 : 50; conjugate class anti-IgG or anti-IgM, AP-labelled. Control band Incubated EUROLINE-WB Anti-Borrelia.

Order No. Formats DY 2131-1601-1 G or M page 84

Automated Evaluation of Incubated Membrane Strips with the System EUROLineScan

• The program EUROLineScan from EUROIMMUN has been developed to enable quantitative evaluation of membrane based test systems, facilitate management of data, and provide detailed documentation of results — tasks which have until now required considerable time. • First, the incubated test strips are scanned using a flatbed scanner or camera system. • EUROLineScan recognizes the position of the strips, even if they have been placed inexactly, identifies the bands, and measures their intensity. The automated evaluation can be monitored, and it is possible to supplement the data manually. • The results are then saved together with the image data. It is no longer necessary to archive (potentially infectious) incubated test strips. A separate results sheet can be produced for each patient.

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Antibodies against Epstein-Barr Virus (EBV) EUROIMMUN Products for Infectious Serology fresh infection

Patient 1: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG) previous infection

Patient 2: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG)

Indirect Immunofluorescence Test: BIOCHIP Sequence EBV • Gold standard for the determination of antibodies against the EBV-CA antigens (Epstein-Barr virus capsid antigen), EBV-EA (Epstein- Barr early antigen) and EBNA (Epstein-Barr nuclear antigen). • Indication: infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma (NPC). • IgG antibodies against EBV-CA indicate an EBV infection. An at least twofold increase in titer and the absence of antibodies against EBNA at the same time is characteristic for the early phase of the infection. IgM antibodies against EBV-CA and antibodies against EBV-EA can also be found in acute infections, but they do not necessarily always occur. The presence of antibodies against EBNA generally indicates the late phase of an EBNA infection. • In cases of an acute EBV infection which cannot be reliably discriminated from a relapse or reinfection, the determination of the antibody avidity using a modified immunofluorescence test as an additional parameter is useful. This requires an additional incubation with urea solution (ZF 1130-0801). The determination of low-avidity antibodies against EBV-CA indicates an acute infection. • For the monospecific confirmation of EBV-CA antibodies in the same test procedure the BIOCHIP containing ECV-CA is supplemented with the antigen substrates gp125 antigen (native) and p19 antigen (recombinant) (EUROPLUS FI 2791-####-20 G or M). • For highly differentiated diagnostics the BIOCHIP Sequence EBV (FI 2799-####-1 X) can be supplemented by using the antigens gp125 and p19 (EUROPLUS FI 2799-####-21 X). • Due to the high prevalence of anti-EBV-CA IgA in NPC patients, the parameter is well suited for screening. Confirmation of the result by determination of IgA antibodies against EBV-EA is recommended. Further anti-EBV test kits for indirect immunofluorescence: Substrate Order No. Substrate Order No. Order No. Formats EBV-CA FI 2791-#### A, G or M EBV-EA FI 2795-#### A or G FI 2799-####-21 X page 148 EBNA FI 2793-#### G EBV-CA & EBV-EA FI 2791-####-2 A or G

Microplate ELISA: Anti-EBV-CA, Anti-EBNA-1, Anti-EBV-EA • Specific confirmatory test for antibodies against EBV-CA, EBNA-1 or EBV-EA. • Indications: infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma. • Serum dilution 1 : 100; conjugate class anti-IgA, -IgG or IgM, POD-labelled. • 1-point calibration, semi-quantitative (IgA, IgM) or 3-point calibration, quantita- tive (IgG). Identical incubation conditions and times: all tests can be combined without difficulty on one and the same microplate. • EBV-CA: native antigen, purified by affinity chromatography; EBNA-1 and EBV-EA: recombinant antigen. • IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption in preparation for the determination of specific IgM class antibodies. Incubated ELISA Anti-EBNA-1. • Available individual ELISA: Antigen Order No. EBV-CA EI 2791-9601 A, G or M EBNA-1 EI 2793-9601 G Order No. (anti-EBNA-1) Formats EI 2793-9601 G page 95 EBV-EA EI 2795-9601 A, G or M

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Antibodies against Epstein-Barr Virus (EBV)

Determination of Low-Avidity Antibodies against EBV-CA

• An alternative principle for the serological diagnosis of fresh infections with EBV 10 has been established by investigating the antibody avidity. E • The first reaction of the immune system following an infection is the formation 8 RAI = with urea Ewithout urea of low-avidity antibodies. As the infection proceeds, increasingly antigen-adapted 6 IgG is formed, and avidity grows. As long as high-avidity IgG is not yet detected Primary Infection

in the serum, it can be assumed that the infection is still in an early stage. 4 Previous Infection • To identify low-avidity antibodies against EBV-CA in a patient’s serum, two microplate ELISA or immunofluorescence tests are performed in parallel: one Number of Patients 2 test is carried out in the conventional way, the other one includes urea treatment 0 between incubations with patient’s serum and peroxidase-labelled anti-human 0 255075100 IgG, resulting in the detachment of low-avidity antibodies from the antigens. Relative Avidity Index (RAI) in % • Low-avidity antibodies against EBV-CA are present if the ELISA extinction is Infectious Serology significantly reduced by urea treatment. For an objective interpretation, the Avidity of antibodies against EBV-CA (IgG)

relative avidity index (RAI) can be calculated out of the measured values with EUROIMMUN Products for and without urea incubation. • With the immunofluorescence test the presence of low-avidity antibodies has Order No. (IIFT) been proved if the test using urea treatment gives a far weaker fluorescence FI 2791-#### X than the two-step test. Order No. (ELISA) Formats EI 2791-####-1 G page 95 and 147

EUROLINE: EBV Profile 2 VCA gp125 • Differentiation of antibodies against Epstein-Barr virus antigens. VCA p19 • Indications: infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal EBNA-1 carcinoma. p22 • Serum dilution 1 : 100; conjugate class anti-human IgG or IgM, AP-labelled. EA-D • With the EUROLINE EBV Profile 2, five different antibodies can be determined: antibodies against VCA gp125, VCA p19, EBNA-1, p22, EA-D. • Recombinant antigens (exception: VCA gp125, native, purified by affinity chro- matography). • EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection. • EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase of Control infection. • EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase of infection with loss of anti-EBNA-1. • Test strips can be automatically incubated and evaluated using the systems Incubated EUROLINE EBV Profile 2. EUROBlotMaster und EUROLineScan (see page 27). Order No. Formats DN 2790-1601-2 G or M page 81

Westernblot: Anti-EBV VCA 125 • Specific confirmatory test for the detection of antibodies against Epstein-Barr EA R virus antigens, differentiation of antibodies against Epstein-Barr virus antigens. EBNA-1 VCA 65 • Indications: infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma. EA D • Serum dilution 1 : 50; conjugate class anti-IgG or anti-IgM, AP-labelled. VCA 40/41/42 • Antigens: whole antigen, SDS extract. VCA 33 • Bands from all specific antigens are included and clearly separated. • EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection. VCA 22 • EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase of infection. • EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase of infection with loss of anti-EBNA-1. • Test strips can be automatically incubated and evaluated using the systems Control band EUROBlotMaster und EUROLineScan (see page 27). Incubated Westernblot Anti-EBV.

Order No. Formats DY 2790-1501 G or M page 85

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Antibodies against Helicobacter pylori

Indirect Immunofluorescence Test: Anti-Helicobacter pylori • Sensitive screening test for the detection of antibodies against Helicobacter pylori. • Indications: gastritis, ulcus ventriculi et duodeni. Late consequences: MALT lymphomas and adenocarcinomas. EUROIMMUN Products for • Initial dilution 1 : 10 (IgM), 1 : 100 (IgG), 1 : 32 (IgA). Infectious Serology • If antibodies against Helicobacter pylori are present, a distinct fluorescence of the bacteria in the smear is obtained. • A positive IgA result correlates well with the activity of a gastritis. An increased IgG antibody titer is considered to be a marker for chronic infections. A signifi- cant drop in the IgG antibody titer about 6 months after therapy is a sign of success. Antibodies against Helicobacter pylori. • The BIOCHIP can be supplemented as required with further substrates, e.g. other infectious agents or tissue sections of primate stomach.

Order No. Formats FI 2080-#### A or G page 134

Microplate ELISA: Anti-Helicobacter pylori • Sensitive screening test for the detection of antibodies against Helicobacter pylori. • Indications: gastritis, ulcus ventriculi et duodeni. Late consequences: MALT lymphomas and adenocarcinomas. • Serum dilution 1 : 100; conjugate class anti-IgA or anti-IgG, POD-labelled. • Antibodies against Helicobacter pylori antigens can be determined quantitatively in RU/ml. • 1-point calibration, semi-quantitative (IgA) or 3-point calibration, quantitative (IgG). Identical incubation conditions and times: both tests can be combined without difficulty on one and the same microplate. • Native antigens. Incubated ELISA Anti-Helicobacter pylori.

Order No. Formats EI 2080-9601 A or G page 91

p 120, CagA EUROLINE-WB: Anti-Helicobacter pylori p 95, VacA • Specific confirmatory test for the detection of antibodies against Helicobacter p 66, UreB pylori. • Indications: gastritis, ulcus ventriculi et duodeni. Late consequences: MALT lymphomas and adenocarcinomas. • Serum dilution 1 : 50; conjugate class anti-IgA or anti-IgG, AP-labelled. p 33 • EUROLINE-WB is a combination of westernblot and line blot techniques. An p 30 SDS extract of a Helicobacter pylori strain is electrophoretically separated p 29, UreA according to molecular mass and transferred onto a nitrocellulose membrane p 26 (westernblot). Two membrane chips coated with highly purified recombinant CagA and VacA are subsequently applied to the westernblot strips. p 19, OMP p 17 • Bands from all specific antigens are included and clearly separated. Alignment bar • Test strips can be automatically incubated and evaluated using the systems EUROBlotMaster und EUROLineScan (see page 27). Control band Incubated EUROLINE-WB Anti-Helicobacter pylori.

Order No. Formats DY 2080-1601-1 A or G page 84

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Antibodies against Herpes Simplex Virus (HSV)

Indirect Immunofluorescence Test: BIOCHIP Mosaic™ HSV-1/HSV-2 • Sensitive screening test for the detection of antibodies against herpes simplex viruses. • Indication: herpes simplex. • Initial dilution 1 : 10 (IgM), 1 : 100 (IgG). • If antibodies against herpes simplex-2 virus are present in the sample, a typical fluorescence of the infected cells is obtained – mainly in the outspread cyto- plasm, less in the cell nuclei. • As HSV-1 and HSV-2 are morphologically and immunologically closely related, cross-reactions can occur. Differentiation may be attempted by testing a serum against both antigen substrates and comparing the titers. • The BIOCHIP Mosaic™ can be supplemented as required with further substrates, e.g. other infectious agents. Antibodies against HSV-1 and HSV-2. Infectious Serology

• Anti-HSV individual tests for indirect immunofluorescence: EUROIMMUN Products for Substrate Order No. HSV-1 FI 2531-#### G or M HSV-2 FI 2532-#### G or M Order No. Formats HSV-1 and -2 FI 2531-####-1 G or M FI 2531-####-1 G or M page 141

Microplate ELISA: Anti-HSV-1, Anti-HSV-2 • Specific confirmatory tests for antibodies against HSV-1 or HSV-2. • Indication: herpes simplex. • Serum dilution 1 : 100; conjugate class anti-IgG or anti-IgM, POD-labelled. • 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative (IgG). Identical incubation conditions and times: all tests can be combined without difficulty on one and the same microplate. • Antigens: type-specific glycoproteins C1 or G2, purified by affinity chromato- graphy. Cross-reactions do not occur. • IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption in preparation for the determination of specific IgM class antibodies. • Available individual ELISA: Incubated ELISA Anti-HSV-1. Antigen Order No. HSV-1 EI 2531-9601-2 G or M HSV-2 EI 2532-9601-2 G or M

HSV-1/2-Pool EI 2531-9601-1 G or M Order No. (anti-HSV-1) Formats EI 2531-9601-2 G or M page 93

EUROLINE-WB: Anti-HSV • Specific confirmatory test for the differentiation of antibodies against HSV-1 and HSV-2. • Indication: herpes simplex. gC 1 • Serum dilution 1 : 50; conjugate class anti-IgG or anti-IgM, AP-labelled. • EUROLINE-WB is a combination of westernblot and line blot techniques. gG 1 Proteins from an SDS extract of HSV-1 are electrophoretically separated according to molecular mass and transferred onto a nitrocellulose membrane. A membrane chip coated with HSV-2 type-specific glycoprotein G2 (gG 2), purified by affinity chromatography, is then added to the westernblot strips. • Bands from all specific antigens are included and clearly separated. gG 2 • The gG 2 band allows the simple differentiation between HSV-1 and HSV-2 infections. Alignment bar • Test strips can be automatically incubated and evaluated using the systems EUROBlotMaster und EUROLineScan (see page 27). Control band Incubated EUROLINE-WB Anti-HSV.

Order No. Formats DY 2531-1601-1 G or M page 85

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Antibodies against Chlamydia

Indirect Immunofluorescence test: Anti-Chlamydia MIF (Micro- Immunofluorescence test) • Serological gold standard for the determination of antibodies against Chlamydia. • Indication: trachoma, urogenital infections, lymphogranuloma venereum, laryn-

EUROIMMUN Products for gitis, sinusitis, bronchitis, pneumonia, psittacosis.

Infectious Serology • Initial dilution 1 : 10 (IgA), 1 : 100 (IgG), 1 : 10 (IgM). • The micro-immunofluorescence test uses purified elementary bodies of the species C. trachomatis, C. pneumoniae and C. psittaci as the antigen. The mutual lipopolysaccharide (LPS) antigen is inactivated to minimise cross reactivity. • The evaluation of the MIF could be significantly facilitated compared to con- ventional test systems by using a cell-based substrate. • The fourth BIOCHIP with non-infected cells allows a reliable differentiation Anti-Chlamydia MIF. between unspecific and specific fluorescence.

Order No. Formats FI 2191-####-3 A, G or M page 138

Microplate ELISA: Anti-Chlamydia trachomatis • Monospecific detection of antibodies against Chlamydia trachomatis. • Indication: trachoma, conjunctivitis, urogenital infections, pneumonia in infants, lymphogranuloma venereum. • Serum dilution 1 : 100, conjugate class anti-human IgA, IgG or IgM, POD- labelled. • 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quanti- tative (IgG). • Antigen: native MOMP antigen (major outer membrane protein). MOMP is a transmembrane protein and represents the main part of the outer membrane of the elementary bodies. Protein purification starts with BGM cells infected with Chlamydia trachomatis of the serotype K. Incubated ELISA Anti-Chlamydia trachomatis. • IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption in preparation for the determination of specific IgM class antibodies.

Order No. Formats EI 2191-9601 A, G or M page 92

Microplate ELISA: Anti-Chlamydia pneumoniae • Monospecific detection of antibodies against Chlamydia pneumoniae. • Indication: laryngitis, sinusitis, bronchitis, pneumonia. • Serum dilution 1: 100, conjugate class anti-human IgA, IgG or IgM, POD-labelled. • 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quanti- tative (IgG). • Antigen: cell lysate from HL cells, strain CDC/CWL-029. • IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption in preparation for the determination of specific IgM class antibodies.

Incubated ELISA Anti-Chlamydia pneumoniae.

Order No. Formats EI 2192-9601 A, G or M page 92

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Antibodies against Emerging Viruses

Indirect Immunofluorescence Test • Over the past years it has been observed that a number of new viruses ("emerging viruses") and other pathogens has spread worldwide, introducing since then unknown diseases into previously unaffected regions. • EUROIMMUN offers a broad spectrum of indirect immunofluorescence tests for the detection of specific antibodies against: Antibodies against SARS CoV, TBE virus, West Nile virus. Pathogen Deisease, syndromes see pag Severe acute respiratory syndrome Corona virus SARS corona virus (SARS-CoV) 142 (SARS) TsBE virus (TBEV), T3ick-borne encephaliti 14 Wsest Nile virus (WNV), W3est Nile fever, encephaliti 14

Jsapanese encephalitis virus (JEV) J0apanese encephaliti 143, 15 Infectious Serology Flaviviruses

Antibodies against Japanese encephalitis virus, EUROIMMUN Products for Yellow fever, hepatitis, haemorrhagic Yellow fever virus (YFV) 143, 144 fever, arthritis Yellow fever virus, Dengue virus. Dengue virus (DENV, types 1-4) D0engue fever, haemorrhagic fever 143, 144, 15 Hantavirus (types Hantaan, HFRS (haemorrhagic fever with renal Puumala, Seoul, Saaremaa, syndrome); HCPS (Hantaviral 147 Dobrava, Sin Nombre and Andes) cardiopulmonary syndrome) Sandfly fever virus (types Sicilian, Pappataci fever, meningitis, 146 Bunyaviruses Naples, Toscana and Cyprus) encephalitis Rift valley fever, haemorrhagic fever, Rift valley fever virus (RVFV) 149 Antibodies against Sandfly fever virus, Hanta- hepatitis virus, Crimean-Congo fever virus. Crimean-Congo fever virus (CCHFV- C9rimean-Congo haemorrhagic fever 14 GPC and -N) Togaviruses Cshikungunya virus (CHIKV) C0hikungunya fever, arthriti 15 Kinetoplastida Lseishmania donovani V9isceral leishmaniasi 13 Palasmodium falciparum M0alaria tropic 140, 15 Haemosporina Palasmodium vivax M0alaria tertian 140, 15 Antibodies against Plasmodium, Rift valley fever • Many of these substrates are available as single substrate with non-infected virus, Chikungunya virus. cells or as useful combinations (syndrome or geographically orientated) for the investigation of serum samples. • IgG absorption as preparatory step for the determination of specific antibodies of class IgM: page 60. • Cross reactions within the virus family, especially with Flaviviruses, should be taken into consideration since they may cause false-positive results. The in- fectious agent can be determined by titration of the sample and comparison of titers.

Microplate ELISA: Anti-TBE Virus, Anti-West Nile Virus, Anti-Dengue Virus • Monospecific determination of antibodies against TBE, West Nile and Dengue virus. • Serum dilution 1: 100, conjugate class anti-human IgG or IgM, POD-labelled. • 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative (IgG). Similar incubation conditions and times: All tests can be combined on one and the same microplate. • IgM test kit with IgG/RF absorbent in the sample buffer for IgG absorption as preparatory step for the determination of specific IgM antibodies. • Available single ELISA:

Incubated ELISA Anti-TBE virus, Anti-WNV, Anti- Antigen Order No. Dengue virus. TBE EI 2661-9601 G or M, avidity, Ab determination in CSF TBE „Vienna“ EI 2661-9601-9 G WNV EI 2662-9601 G or M, avidity Order No. (Anti-FSME) Formats Dengue EI 266b-9601 G or M EI 2661-9601 G or M page 94

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BIOCHIP Mosaics™ for Infectious Serology (For formats see pages 149-150)

FI 2821-1001-1 G FI 2822-1001-1 G RESPIRATORY TRACT PROFILE 1 EXANTHEMA PROFILE 1 IgG IgM IgG IgM Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10

EUROIMMUN Products for V Verification BIOCHIP*** V Verification BIOCHIP*** 1. RSV 1. HHV-6 Infectious Serology 2. Adenovirus type 3 2. Rubella virus* 3. Influenza virus type A (H1N1) 3. Measles virus 4. Influenza virus type A (H3N2) 4. Mumps virus Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 5. Influenza virus type B 5. VZV 6. Parainfluenza virus type 1 6. EBV-CA** 7. Parainfluenza virus type 2 7. EBV-EA 8. Parainfluenza virus type 3 8. Treponema pallidum Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10 9. Parainfluenza virus type 4 9. HSV-1 10. Bordetella pertussis** 10. HSV-2 11. Bordetella parapertussis** 11. Coxsackie virus type B1 12. Mycoplasma pneumoniae 12. Coxsackie virus type A9 Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 10 13. Coxsackie virus type B1 13. Echo virus type 7 14. Coxsackie virus type A7 14. Borrelia afzelii 15. Echo virus type 7 15. Borrelia burgdorferi sensu stricto (CH) 16. Chlamydia pneumoniae 16. Borrelia garinii Field E 1 : 100 1 : 100 Field E 1 : 100 1 : 100 17. Haemophilus influenzae*,** 17. CMV 18. Klebsiella pneumoniae* 18. Candida albicans** 19. Legionella pneumophila serotype 1*,** 19. Candida krusei*,** 20. Legionella pneumophila serotype 12*,** 20. Candida tropicalis*,**

FI 2823-1001-1 G FI 2824-1001-1 G LYMPHADENITIS PROFILE 1 CENTRAL NERVOUS SYSTEM PROFILE 1 IgG IgM IgG IgM Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 V Verification BIOCHIP*** V Verification BIOCHIP*** 1. HIV-1* 1. Rubella virus* 2. HIV-2* 2. Measles virus 3. HHV-6 3. Mumps virus 4. Rubella virus* 4. VZV Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 5. Measles virus 5. Adenovirus type 3 6. Mumps virus 6. EBV-CA** 7. Adenovirus type 3 7. Treponema pallidum 8. Parainfluenza virus type 1 8. Toxoplasma gondii** Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10 9. EBV-CA** 9. HSV-1 10. EBV-EA 10. HSV-2 11. Toxoplasma gondii** 11. Coxsackie virus type B1 12. Treponema pallidum 12. Coxsackie virus type A7 Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 10 13. HSV-1 13. Echo virus type 7 14. HSV-2 14. Borrelia afzelii 15. CMV** 15. Borrelia burgdorferi sensu stricto (CH) 16. Coxsackie virus type B5 16. Borrelia garinii Field E 1 : 100 1 : 10 Field E 1 : 100 1 : 100 17. Coxsackie virus type A9 17. CMV 18. Bartonella henselae** 18. Haemophilus influenzae*,** 19. Chlamydia trachomatis** 19. Listeria monocytogenes 1/2a* 20. Chlamydia pneumoniae 20. Listeria monocytogenes 4b* * For clinical evaluation the results must be confirmed with a CE approved test. ** For practical reasons the recommended incubation differs from the standard incubation for this substrate. *** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction. BIOCHIP Mosaics™ containing fewer substrates can be produced upon request.

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Produktkatalog2010.p65 58 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG

BIOCHIP Mosaics™ for Infectious Serology (For formats see pages 149-150)

FI 2825-1001-1 G FI 2826-1001-1 G MYOCARDITIS PROFILE 1 INFECTIOUS ARTHRITIS PROFILE 1 IgG IgM IgG IgM Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 V Verification BIOCHIP*** V Verification BIOCHIP*** 1. Mumps virus 1. VZV 2. Adenovirus type 3 2. Influenza virus type A (H1N1) 3. Influenza virus type A (H1N1) 3. Influenza virus type A (H3N2) 4. Influenza virus type A (H3N2) 4. Influenza virus type B Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 5. Influenza virus type B 5. Yersinia enterocolitica O:3*,** 6. Parainfluenza virus type 1 6. Yersinia enterocolitica O:6*,** ,

7. Parainfluenza virus type 2 7. Yersinia enterocolitica O:9* ** Infectious Serology 8. Mycoplasma pneumoniae 8. Toxoplasma gondii** EUROIMMUN Products for Field C 1 : 100 1 : 10 Field C 1 : 100 1 : 10 9. CMV** 9. Borrelia afzelii 10. Coxsackie virus type B1 10. Borrelia burgdorferi sensu stricto (CH) 11. Coxsackie virus type A16 11. Borrelia garinii 12. Echo virus type 7 12. Chlamydia trachomatis** Field D 1 : 100 1 : 10 13. Borrelia afzelii 14. Borrelia burgdorferi sensu stricto (CH) 15. Borrelia garinii 16. Chlamydia pneumoniae

FI 2827-1001-1 G FI 2828-1001-1 G GASTROINTESTINAL TRACT PROFILE 1 ACCOMPANYING HEPATITIS PROFILE 1 IgG IgM IgG IgM Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 V Verification BIOCHIP*** V Verification BIOCHIP*** 1. Adenovirus type 3 1. Adenovirus type 3 2. Yersinia enterocolitica O:3*,** 2. EBV-CA** 3. Yersinia enterocolitica O:6*,** 3. EBV-EA 4. Yersinia enterocolitica O:9*,** 4. Toxoplasma gondii** Field B 1 : 100 1 : 10 Field B 1 : 100 1 : 10 5. Coxsackie virus type B3 5. HSV-1 6. Coxsackie virus type A7 6. HSV-2 7. Echo virus type 7 7. CMV** 8. Campylobacter jejuni*,** 8. Coxsackie virus type B5 Field C 1 : 100 1 : 100 Field C 1 : 10 1 : 10 9. Campylobacter coli*,** 9. Coxsackie virus type A9 10. Helicobacter pylori** 10. Echo virus Typ 7 11. Klebsiella pneumoniae* 11. Echinococcus granulosus** 12. Candida albicans**

FI 2829-1001-1 G FI 2831-1001-1 G OPHTHALMOLOGY PROFILE 1 PREGNANCY PROFILE 1 IgG IgM IgG IgM Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 V Verification BIOCHIP*** V Verification BIOCHIP*** 1. Measeles virus 1. Rubella virus* 2. VZV 2. Toxoplasma gondii** 3. Adenovirus type 3 3. HIV-1* 4. Toxoplasma gondii** 4. HIV-2* Field B 1 : 100 1 : 10 Field B 1 : 100 1 : 10 5. HSV-1 5. Chlamydia trachomatis** 6. HSV-2 6. CMV** 7. Coxsackie virus type A24 7. HSV-2 8. Chlamydia trachomatis** 8. VZV** * For clinical evaluation the results must be confirmed with a CE approved test. ** For practical reasons the recommended incubation differs from the standard incubation for this substrate. *** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction. BIOCHIP Mosaics™ containing fewer substrates can be produced upon request.

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Produktkatalog2010.p65 59 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG

Additional Reagents for the Determination of Acute Infections

IgG Absorpion • Before a patient’s serum is tested for specific antibodies of the IgM class, anti- bodies of class IgG must be removed by ultracentrifugation, chromatography or immunoabsorption. rheumatoid factor • Specifically bound IgG would displace IgM from the antigen leading to false IgM EUROIMMUN Products for negative test results. Infectious Serology • Moreover, the absorption prevents any IgM class rheumatoid factors present from reacting with specifically bound IgG and thus leading to false IgM positive test results. • Indication: an IgG absorption of serum samples should always be performed for all IgM antibody determinations in infectious serology before incubating the sera.

IgG

absorbent

EUROSORB IgG/RF Absorbent for Indirect Immunofluorescence • Functional principle: the EUROSORB reagent contains an anti-human IgG anti- body preparation from goat. Immunoglobulin G of a serum or plasma sample is bound with high specificity by these antibodies and precipitated. If the sample also contains rheumatoid factors, these will be absorbed by the anti-human IgG/ IgG complex. • Incubation time of the sample with the reagent is 15 minutes. A centrifugation step for a subsequent investigation by immunofluorescence is recommended. • All IgG subclasses are bound and precipitated by the anti-human IgG antibodies. • Human serum IgG in concentrations of up to 15 mg/ml and rheumatoid factors are completely removed by the absorbent (average serum IgG concentration in adults: 12 mg/ml). • The recovery rate of the IgM fraction is almost 100%. EUROSORB IgG/RF Absorbent. • One unit contains 4.5 ml absorbent, sufficient for the absorption of 100 serum samples.

Order No. Formats ZF 1270-0145 page 152

Urea Solutions and Avidity Buffers for the Determination of Low- Avidity Antibodies in Infectious Serology • To identify low-avidity antibodies in a patient’s serum, two immunofluorescence tests are performed in parallel: one test is carried out in the conventional way, the other one includes urea treatment between incubations with patient’s serum and peroxidase-labelled anti-human IgG, resulting in the detachment of low- avidity antibodies from the antigens. • Low-avidity antibodies are present if the fluorescence intensity is significantly reduced (two intensity levels ore more) by urea treatment. • The following reagents for avidity determination are available: IFT, Ab against Order No. Avidity Solution Incubation Time Rubella ZF 1130-0501 urea solution, 5 M 10 min Reagents for determination of low-avidity anti- WNV ZF 1130-0601 urea solution, 6 M 10 min bodies in infectious serology. Toxoplasma gondii ZF 1130-0801 urea solution, 8 M 10 min EBV-EA, EBV-CA ZF 1130-0801 urea solution, 8 M 30 min CMV ZF 1131-0101-1 avidity buffer 1 10 min Order No. Formats VZV ZF 1131-0101-2 avidity buffer 2 30 min ZF 1130 und ZF 1131 page 152

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Produktkatalog2010.p65 60 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG Allergology EUROIMMUN Products for EUROIMMUN PRODUCTS FOR ALLERGOLOGY

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Produktkatalog2010.p65 61 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG

Antibodies of Class IgE against Allergens

EUROLINE: Specific IgE grasses • Determination of specific IgE in serum. • Indication: Clarification of allergic reactions to inhalation allergens, food trees allergens and cross-reactive allergens (pollen-associated food allergies). weeds • Serum dilution: undiluted (or 1 : 10); conjugate class anti-IgE (monoclonal), AP- labelled. mites • Calibration: 3 indicator bands on each strip for semiquantitative evaluation. animal hair • Antibodies against up to 20 allergens per strip can be simultaneously mono-

EUROIMMUN Products for specifically detected. mould spores • EUROLINE profiles with different allergen compositions are available for various indicators test requirements: atopy, inhalation, food and cross reactions. Allergology • The program EUROLineScan from EUROIMMUN has been developed to enable quantitative evaluation of EUROLINE analyses, facilitate management of data, and provide detailed documentation of results. Incubated EUROLINE Allergy Profile Inhalation. • The incubated EUROLINE test strips are scanned using a flatbed scanner. EUROLineScan recognizes the position of the strips, even if they have been placed inexactly, identifies the bands, and measures their intensity. Order No. (Inhalation) Formats DP 3110-1601 E Page 82

EUROIMMUN Microplate ELISA: Total IgE • Determination of the total IgE concentration in serum. • Indications: Differentiation between allergic and intrinsic asthma, between allergic and vasomotor rhinitis, and between atopic and seborrhoic dermatitis. • Serum dilution 1 : 10; conjugate class anti-IgE (monoclonal), POD-labelled. • One microplate well incubated per patient. • 4-point calibration, quantitative. • Coating: anti-human IgE, polyclonal. • The Total IgE ELISA serves as a screening test for allergy diagnostics and provides an indication for the presence of an allergic reaction.

Incubated ELISA Total IgE.

Order No. Formats EV 3840-9601 E Page 95

Allercoat™ 6 Microplate ELISA: Specific IgE • Determination of allergen-specific IgE concentrations in serum. • Indication: identification of allergic reactions to more than 600 different allergens and allergen mixtures. • Serum dilution: undiluted, conjugate class anti-human IgE, AP-labelled. • One microplate well per allergen/allergen mixture is incubated for each patient. • Calibration: 6-point calibration, quantitative; using reference preparation 2 IRP 75/502 from the WHO. • The allergens are coupled to paper rings and can be flexibly configured for each sample according to the analysis. • Customized pre-assembled microplates with individual allergy parameters are available on request (Order no.: EP 9901-0101). Orders can be made online with AllercoatTM 6 ELISA. the provided software. Please contact us! • A light table and special evaluation software are available to supplement the simple manual Allercoat™ 6 ELISA procedure. • Allercoat™ 6 ELISA are automatable using the EUROIMMUN Analyzer I and the EUROIMMUN Allercoat software. Order No. Formats EP ####-0110 E Page 96-115

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Produktkatalog2010.p65 62 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG

Antibodies of Class IgE against Allergens

Customized Laboratory Software for Flexible Automation of Allercoat™ System • Convenient online ordering of individual pre-prepared Allercoat™ microtiter plates. • Integrated light table for manual preparation of ELISA plates and sample distribution. • Direct control of photometer, automated evaluation via calibration curve and compilation of results. • Fully automated incubation of samples and evaluation of results via connection to the EUROIMMUN Analyzer I. • Fully automated administration, documentation and archiving of all data. • Simple operation using graphic user commands and clear presentation of the most important information at a glance. AllercoatTM Software. • Connection to commonly used laboratory systems for convenient transfer of requests and results. Allergology • Additional security through user administration with individual access rights and confirmation step before results editing. EUROIMMUN Products for

Individual equipment allergen rings with allergen rings

undiluted Pipette: 50 µl per well samples

Incubate: 60 min, 37 °C

Wash: 300 µl wash buffer per well 4x

enzyme conjugate Pipette: 50 µl per well

Incubate: 60 min, 37 °C

Wash: 300 µl wash buffer per well Fitting of allergen rings into 8x microplate wells

chromogen-/ Pipette: 100 µl per well substrate sol.

Incubate: 30 min, 37 °C

yyy


yyy

yy stop Pipette: 100 µl per well solution

yy

yyy


yyy

yy

yyy


yyy

yy Evaluate: photometric measurement


yyy


yyy

yy

at a wavelength of 405 nm


yyy


yyy

yy

yyy


yyy

yy

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Produktkatalog2010.p65 63 30.10.2009, 09:48 Medizinische Labordiagnostika EUROIMMUN AG

General Delivery Conditions

Products from EUROIMMUN AG will be delivered according to the following conditions, as long as no other conditions have been agreed in writing. On issuing an order, the buyer acknowledges the delivery conditions. EUROIMMUN does not accept the sales conditions of the buyer, even when EUROIMMUN has not expressly contradicted them. Contract terms are valid for all future business connection even if they have not been expressly agreed upon again.

Orders: Orders to EUROIMMUN can be made in writing (including electronic communication) or verbally. Verbally issued orders first become legally binding for EUROIMMUN with a written confirmation from the orderer or with the delivery of goods.

Delivery: EUROIMMUN generally delivers to end users within 7 days of order receipt and to distributors within 14 days, but is not tied to any definite delivery period. If a delivery is not possible through unforseeable circumstances (e.g., factory disruptions, raw material delivery delays, transport difficulties, strikes), the delivery obligation does not apply. EUROIMMUN reserves the right to deliver in part. The delivery obligation of EUROIMMUN AG ceases as long as the customer is in arrears. EUROIMMUN chooses the packing and dispatching method at its own discretion, according to the respective requirements.

Product characteristics: The delivered products comply with specifications given in the product catalogue, on the product itself, or in the supplied information sheets. If specifications are inconsistent, the labels on the product itself and the details in the information sheet provided with the product apply. After the given expiration date has passed, the test reagents must not be used.

EUROIMMUN products must only be used for the intended purpose. It is the buyer’s responsibility to check the functional capability immediately on receipt of the product as well as on every day of usage. In particular, the functioning of test reagents can be perturbed through causes outside the direct influence of the maunfacturer, for example, through suboptimal transportation, incorrect storage, or incorrect usage. When test reagents delivered from EUROIMMUN are used, the user must supervise the analysis with appropriate proficiency.

Warranty and liability: If nothing else has been agreed upon in writing, all risks pass to the buyer as soon as the goods have been delivered to the carrier or has left EUROIMMUN AG premises for dispatch. With notification of dispatch by EUROIMMUN the risk passes to the buyer if the delivery is postponed or delayed by request of the buyer. On receipt of the goods, the buyer has one working day to check if they are in accordance with the nature and quantity of the agreement and if the goods are free from visible defects. If any complaints arise from this inspection, they should be communicated to EUROIMMUN AG in writing within 2 working days. Hidden defects or functional faults that were not identifiable with the initial inspection and are later discovered should be communicated to EUROIMMUN AG in writing within 14 days of receipt of the goods. If no complaints are received within the stipulated period, it is assumed that the goods are of appropriate quality and quantity for the customer. Complaints do not release the buyer from payment obligation.

With prompt and reasonable complaints on the grounds of product defects or the delivery of something other than the ordered goods, EUROIMMUN is obliged to exchange or amend the goods within 14 days or to withdraw or reimbourse the payment, as it chooses. If the defect is not corrected in spite of delivery of a replacement or an amended product, the buyer can demand that the sale is cancelled.

If defects are promptly reclaimed, EUROIMMUN has the choice between a further delivery or an appropriate credit note. Further compensatory claims from the buyer are excluded, as long as EUROIMMUN has not violated its contractual or legal obligations through outright negligence or by intention. In such cases EUROIMMUN provides compensation of up to a maximum of 20 times the price of one packet (test kit) of the defective product. EUROIMMUN takes no responsibility for any damage resulting from faulty goods.

Prices: Prices from the official EUROIMMUN pricelist in the country of the buyer are applicable. Invoices are provided in the agreed currency. Prices are “ex works”. Expenses for packing and freight as well as for cooling during transport are added on, including costs for the disposal of packaging material by the customer. Statutory value added tax is not included in the list prices.

Payment terms: Payment obligations in countries of export must be settled within 30 days after recieving the goods. No cash discounts will be given unless agreed in writing. Payments by cash transfer or check are valid from the timepoint that the invoice amount is credited to a EUROIMMUN AG bank account. In cases of payment arrears, EUROIMMUN reserves the right to charge compensatory interest of 10% p.a., applicable from the settlement date, without any further notice. In special cases EUROIMMUN can arrange alternative payment periods or demand advance payments. EUROIMMUN’s demands resulting from an order cannot be offset by the customer through counter demands.

Ownership rights: The delivered goods remain the property of EUROIMMUN AG until full payment. Selling on of EUROIMMUN products is only permitted for companys who are authorized in writing from EUROIMMUN to do so. Software received from EUROIMMUN should not be passed on to third parties without written permission from EUROIMMUN AG.

Consultation: Advice from EUROIMMUN AG, although provided to the best knowledge, is nevertheless not binding. No liability claims can ensue from erroneous advice.

Applicable law, place of jurisdiction, ineffective regulations: The contract conditions are subject to the laws of the Federal Republic of Germany. The United Nations Conventions on Contracts for the International Sale of Goods does not apply. The place of jurisdiction and fulfilment is Luebeck. If any provision of these general delivery conditions will be held invalid or unenforcable, this general delivery condition will not be rendered invalid as a whole, and the provisions will be changed and interpreted so as best to accomplish the objective of the unenforcable or invalid provision.

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Produktkatalog2010.p65 153 04.11.2009, 12:40 Medizinische Labordiagnostika EUROIMMUN AG

Index Autoantibody Diagnostics reticulin ...... 14, 17, 131-133 acetylcholine receptor (ACHR) ...... 12, 17, 89 retina ...... 13-14, 17, 118 actin ...... 16, 17, 32, 38, 47, 68, 122, 129 rheumatoid factors ...... 36, 60 adrenal cortex ...... 13, 17, 45, 66, 116 Ri ...... 17, 42-43, 66, 80, 83, 116-118 agglutination test ...... 89 RIA ...... 16, 30, 35, 40, 44, 86-90 AMA ...... 6, 13, 16-17, 26, 33, 37-40, 45, 47, 68, 79, 116, 122, 126-131 ribosomal P-proteins ...... 14, 16, 32, 68, 88 amphiphysin ...... 17, 42, 80, 117-118 RNS-Polymerase ...... 14, 16, 32, 47 ANA ...... 14, 16-17, 26, 32-34, 37-38, 42, 46-47, 68, 80, 87, 118-124, 126-131 Ro-52 ...... 16-17, 26, 32-34, 39, 47, 79-80, 83, 87 ANCA ...... 12-14, 16-17, 32, 46-47, 66-67, 86, 119-121, 123-124 Sa ...... 16, 36, 87 aquaporin ...... 12, 17, 42, 66, 118 Saccharomyces cerevisiae ...... 15, 17, 76, 95, 101, 123-124 ASCA ...... 15, 17, 76, 95, 101, 123-124 Scl-70 ...... 14, 16, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127 ASMA ...... 12, 16-17, 37-38, 68, 117-118, 123-126, 128-131 skeletal muscle ...... 12-14, 17, 38, 122, 124, 130 Autoantibody Profile 2 ...... 128 SLA/LP ...... 17, 26, 32, 38-39, 79-80, 86 basement membrane ...... 12, 16-17, 46, 67, 80, 86, 120-121 Sm ...... 14, 16, 24, 26, 32-34, 47, 68, 79-80, 87, 126-127 ß2-glycoprotein ...... 88 smooth muscles ...... 12, 16-17, 38, 67, 117-118, 123-126 bile ducts ...... 17, 32 Sp100 ...... 17, 26, 38-39, 68, 80 BP180 ...... 12, 17, 41, 87, 125 spermatozoa ...... 14, 17, 66, 86, 89, 117 BP230 ...... 12, 17, 41, 87, 125 spindle fibers ...... 16, 32, 47, 68 BPI ...... 17, 46-47, 86 SS-A ...... 6, 14, 16-17, 24, 26, 32-34, 47, 68, 79-80, 83, 87, 126-127 brain ...... 12, 66, 116-117 SS-B ...... 6, 14, 16-17, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127 C1q ...... 16, 87, 88 ssDNA ...... 14, 16-17, 34, 47, 87 cANCA ...... 12, 16-17, 32, 46-47, 66, 86, 119-121, 123 TAb ...... 17, 40, 66, 116 cardiolipin (AMA M1) ...... 16-17, 84, 88 testis ...... 14, 17, 40, 43, 66, 116-117 cartilage ...... 16, 124 thrombocyte antigens ...... 14, 17, 67, 121 cathepsin G ...... 17, 46-47, 86 thyroglobulin (TG) ...... 14, 17, 40, 45, 66, 79, 86, 89, 90, 116 cell nuclei (ANA global test) .... 14, 16-17,26, 32-34, 37-38, 42, 46-47, 68, 80, 87,118-124, 126-131 thyroid gland ...... 14, 17, 40, 45, 66, 86, 89, 116 centromere ...... 14, 16, 32, 34, 47, 68, 87-88 thyroid peroxidase (TPO) ...... 17, 40, 79, 86, 89 cerebellum ...... 12-14, 42-44, 83, 116-118 TRAb ...... 17, 40, 86, 89 circulating immune complexes (CIC) ...... 16, 35, 88 transglutaminase ...... 17, 48, 88 cyclic citrullinated peptide (CCP) ...... 16, 36, 87 U1-nRNP ...... 14, 16, 68, 87 cyclin I (PCNA) ...... 12, 16, 26, 32, 47, 68, 80, 87 vascular endothelium ...... 16, 17, 69 cyclin II (mitosin) ...... 12, 47, 68 vimentin ...... 14, 16, 47, 68 cytoplasm of granulocytes ...... 12-14, 16-17, 32, 46-47, 66-67, 86, 119-121, 123-124 Yo ...... 14, 17, 42-43, 66, 80, 83, 116-118 desmoglein ...... 12, 17, 41, 87, 124, 125 zona pellucida ...... 17, 66, 86, 89 desmosomes ...... 12, 17, 41, 67, 125 dsDNA ...... 6, 12, 16-17, 26, 32-35, 38, 42, 47, 68, 79-80, 87, 89, 128, 130, 151 Infectious serology elastase ...... 17, 46-47, 86 Adenovirus ...... 15, 18, 58-59, 74-75, 94,144 elastin ...... 12, 16-17, 69 Afipia felis ...... 15,18 ENA ...... 16, 24, 32, 34, 79-80, 87 Bartonella ...... 15, 18, 58, 71, 72, 138 endomysium ...... 12, 17, 32, 48, 69, 88, 131-133 Bordetella ...... 15, 18, 58, 70, 81, 91, 134 endothelial cells ...... 12, 16-17, 32, 69, 133 Borrelia ...... 15-18, 21, 28, 50-51, 58-59, 70-71, 77, 81, 84, 91, 135-136 epidermis ...... 12-13, 17, 67, 125 Brucella abortus ...... 92 EUROArray ...... 89 Campylobacter ...... 15, 18, 59, 70, 91, 134 EUROPLUS ...... 7, 12, 32, 37-41, 46-48, 50, 52, 116, 120-123, 126-127, 129, 131-136, 140, 148 Candida ...... 15, 18, 58-59, 76, 108, 150 eye antigens ...... 118 Chikungunya virus ...... 15, 57, 76, 150 F-actin ...... 17, 38, 68, 122, 129 Chlamydia ...... 15-16, 18, 56, 58-59, 71, 92, 137-138 GAD ...... 12, 17, 42, 44, 66, 86, 89, 116 Coxsackie virus ...... 15, 18, 58-59, 75, 145-146 gangliosides ...... 17, 80 Crimean Congo fever virus ...... 57, 76, 149 gliadin ...... 7,12, 17, 48, 69, 76, 95, 101, 131-133, 151 Cytomegalovirus (CMV) ...... 7, 15, 21, 58-60, 73, 81, 85, 93, 142, 151 glomerular basement membrane (GBM) ...... 12, 17, 46, 67, 80, 86, 120-121 Dengue virus ...... 15, 57, 74, 94, 143-144, 150 glutamate receptor ...... 12, 17, 43, 66,118 EBNA ...... 15, 18, 52-53, 76,81, 95, 148 glutamic acid decarboxylase ...... 12, 17, 42, 44, 66, 86, 89, 116 EBV-CA ...... 7, 15, 18, 21, 52-53, 58-60, 75-76, 95, 147-148 Golgi apparatus ...... 12, 16, 32, 47, 68 EBV-EA ...... 7, 18, 52, 58-60, 76, 95, 147-148 goblet cells ...... 12, 17, 67, 123-124 Echinococcus granulosus ...... 15, 18, 82, 88, 106, 136 heart muscle ...... 12, 17, 124, 130 Echo virus ...... 15, 18, 58-59, 75, 146 HEp-2-cells ...... 6, 12-14, 32-33, 35, 37-38, 44-45, 81, 114-118, 121-126 Epstein-Barr virus capsid ag ...... 7, 15, 18, 21, 52-53, 58-60, 75-76, 78, 81, 85, 95, 147-148, 152 histones ...... 6, 13, 16, 26, 32-34, 47, 79-80, 87 EUROPLUS ...... 7, 12, 32, 37-41, 46-48, 50, 52, 116, 120-123, 126-127, 129, 131-136, 140, 148 Hu ...... 13, 17, 42-43, 66, 80, 83, 116-118 EUROSORB IgG/RF absorbens ...... 60, 64, 152 HUVEC ...... 133 Haemophilus influenzae ...... 15, 18, 58, 70, 134 hypothalamus antigens ...... 13, 117 Hantavirus ...... 15, 57, 75, 81, 95, 147 IA-2 ...... 17, 44, 89 Helicobacter pylori ...... 15, 18, 54, 59, 70, 77, 84, 91, 134 insulin ...... 17, 44, 89 Herpes simplex (HSV) ...... 15, 18, 21, 55, 58-59, 73, 78, 81, 85, 92-93, 140-141 intestinal goblet cells ...... 12, 17, 67, 123-124 HHV-6 ...... 15, 18, 58, 73, 141 intrinsic factor ...... 13, 17, 45, 67, 86, 122-123 HIV ...... 15, 18, 36, 58-59, 72-73, 140-141 Jo-1 ...... 13, 16, 24, 26, 32-34, 47, 68, 79-80, 87-88, 126-127 Influenza virus ...... 15, 58-59, 70, 75, 94-95, 134, 144-145 keratin ...... 12, 13, 16-17, 36, 67, 125 Japanese encephalitis virus ...... 57, 74, 143,150 Ku ...... 13, 16, 26, 33, 47, 68, 80 Klebsiella pneumoniae ...... 15, 18, 58-59, 70, 134 lactoferrin ...... 17, 46-47, 67, 86, 121, 124 Legionella ...... 15, 18, 58, 71, 91, 136-137 latex agglutination test ...... 89 Leishmania ...... 15, 18, 57, 72, 139 LC-1 ...... 17, 26, 32, 38-39, 79-80, 83 Listeria ...... 15, 18, 58, 71, 136 Leydig cells ...... 17, 43, 64, 112-113 Measles virus ...... 15, 18, 21, 58-59, 64, 73, 93, 142 liver-kidney microsomes (LKM) ...... 13, 17, 37-38, 67, 116, 122, 126-131 Mumps virus ...... …15, 18, 21, 58-59, 73, 93, 142 liver-specific antigens ...... 13, 17, 32, 38, 67, 121 Mycoplasma ...... 15, 18, 58-59, 72, 92, 139 LKM-1 ...... 17, 26, 32, 39, 79-80, 86 Parainfluenza virus ...... 15, 58-59, 75, 95, 145 lung alveoli ...... 17, 121 Parvovirus ...... 36, 93 lymphocyte antigens ...... 13, 17, 121 Plasmodium ...... 7, 15, 18, 57, 140, 150 M2 antigen (AMA-M2) ...... 6, 17, 26, 33, 37-39, 68, 79-80, 88 Reiter spirochetes ...... 70 M4 antigen ...... 13, 17, 32, 37, 79, 108 Respiratory syncytial virus (RSV) ...... 15, 18, 58, 74, 94, 144 M9 antigen ...... 13, 17, 32, 37, 68, 79, 108 Rift valley fever virus ...... 57, 74, 149 Mab ...... 17, 40, 66, 116 Rubella virus ...... 7, 15, 18, 21, 73, 81, 85, 93, 140, 142, 149 MAG ...... 13, 17, 42, 66 Sandfly fever viris ...... 57 Mi-2 ...... 13, 16, 26, 33, 47, 80 SARS coronavirus ...... 57, 142 mitochondria (AMA) ...... 6, 13, 16-17, 26, 33, 37-40, 45, 47, 68, 79, 116, 122, 126-131 TBE virus ...... 15, 18, 21, 48, 55, 72, 90, 138-139 mitosin (cyclin II) ...... 12, 47, 68 Toxoplasma gondii ...... 7, 15, 18, 21, 57-60, 72, 81, 92, 140 myelin ...... 12-13, 17, 42, 66 Treponema pallidum ...... 15, 18, 58, 70, 77, 84, 91 myeloperoxidase (MPO) ...... 13, 17, 46-47, 79-80, 86, 120 Ureaplasma urealyticum ...... 15, 18, 72, 139 nDNA ...... 6, 12, 16-17, 26, 32-35, 38, 42, 47, 68, 79-80, 87, 89, 128, 130, 151 Varicella zoster virus (VZV) ...... 15, 21, 58-60, 73-74, 93-94, 143 nerves ...... 12-14, 17, 42, 66, 117-118 VlsE ...... 15, 28, 50-51, 70, 81, 84, 91, 135-136 neuronal autoantibodies ...... 17, 42-43, 80, 83 West Nile virus ...... 7, 15, 21, 57, 74, 94, 143 NMDA receptor ...... 12, 17, 43, 66, 118 Yellow fever virus ...... 57, 74, 143 -144 NMO ...... 17, 42, 118 Yersinia enterocolitica ...... 15-16, 18, 59, 71, 78, 84, 91-92, 137 nRNP/Sm ...... 16, 24, 26, 32-34, 47, 79-80, 87, 126-127 nuclear membrane ...... 17, 32, 47, 68 Allergology nucleosomes ...... 16, 32-33, 35, 47, 79-80, 87 animal allergens ...... 19, 98-99 oesophagus ...... 12-13, 41, 48, 125, 131-132 environmental allergens ...... 19,112-113 ovarial antigens ...... 45, 86, 89, 116 food ...... 19, 62, 82-83, 100-10 P/Q calcium channel (VGCC) ...... 17, 89 further allergens ...... 110 pANCA ...... 13, 16-17, 32, 46-47, 67, 86, 119-121, 123-124 grasses ...... 19, 62,107 pancreas islets ...... 114, 44-45, 66, 116, 118 herbal and flower pollen ...... 19, 62, 102, 114-115 parathyroid gland ...... 13, 17, 116 house dust ...... 19, 108 parietal cells (PCA) ...... 12, 17, 45, 67, 86, 116, 122-123 insects ...... 19, 39, 48, 83, 86, 88, 95, 108 parotid gland excretory ducts and acini ...... 14, 17, 124 mites ...... 19, 62, 98, 108 PCNA (cyclin I) ...... 12, 16, 26, 32, 47, 68, 80, 87 moulds ...... 19,108-110 phosphatidylserine ...... 16, 88 parasites ...... 18-19,110 phospholipids ...... 16, 108 pharmaceutical drugs ...... 19, 96-97 pituitary gland antigens ...... 13, 17, 117 trees ...... 19, 110-111 PL-12 ...... 16, 26, 33, 47, 80 PL-7 ...... 16, 26, 33, 47, 80 Automation placenta ...... 14, 17, 117 EUROBlotMaster ...... 26-27, 29 PM-Scl ...... 6, 16, 26, 32-34, 47, 79-80, 87 EUROIMMUN Analyzer ...... 22, 62-63 proteinase 3 (PR3) ...... 7, 14, 17, 46-47, 66, 79-80, 86, 120 EUROLineScan ...... 4, 26-29, 51, 62 proteinase 3 (capture test) ...... 46, 86 EUROStar ...... 8 renal glomeruli (GBM) ...... 12, 17, 46, 67, 80, 86, 120-121 instruments ...... 8, 22, 27

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IIFT

ELISA

Immunoblots EUROLabOffice

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