DOCSLIB.ORG

Immunoglobulin M Memory B Cell Decrease in Inflammatory Bowel Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immunoglobulin M Memory B Cell Decrease in Inflammatory Bowel Disease European Review for Medical and Pharmacological Sciences 2004; 8: 199-203 Immunoglobulin M memory B cell decrease in inflammatory bowel disease A. DI SABATINO, R. CARSETTI**, M.M. ROSADO**, R. CICCOCIOPPO, P. CAZZOLA, R. MORERA, F.P. TINOZZI*, S. TINOZZI*, G.R. CORAZZA Gastroenterology Unit and *Department of Surgery, IRCCS Policlinico S. Matteo, University of Pavia – Pavia (Italy) **Research Center Ospedale Bambino Gesù – Rome (Italy) Abstract. – Background & Objectives: Abbreviation list Memory B cells represent 30-60% of the B cell pool and can be subdivided in IgM memory and CAI = Clinical activity index switched memory. IgM memory B cells differ from CDAI = Crohn’s disease activity index switched because they express IgM and their fre- quency may vary from 20-50% of the total memo- Ig = Immunoglobulin ry pool. Switched memory express IgG, IgA or IgE and lack surface expression of IgM and IgD. Switched memory B cells derive from the germi- nal centres, whereas IgM memory B cells, which require the spleen for their survival and/or gener- Introduction ation, are involved in the immune response to en- capsulated bacteria. Since infections are one of the most frequent comorbid conditions in inflam- Several studies have focused on the mecha- matory bowel disease, we aimed to verify whether nisms that regulate T cell survival, differenti- IgM memory B cell pool was decreased in ation and activation in inflammatory bowel Crohn’s disease and ulcerative colitis patients. disease1,2, but very little is known about B Patients & Methods: Peripheral blood sam- ples were obtained from 22 Crohn’s disease pa- cells and their function. MacDermott et al. tients, 20 ulcerative colitis patients, 22 healthy have shown that immunoglobulin (Ig) synthe- controls and 18 splenectomized patients. To sis and secretion by peripheral blood and in- analyse peripheral blood lymphocytes, flow cy- testinal mononuclear cells are changed in pa- tometry was performed using anti-CD19, anti- tients with Crohn’s disease and ulcerative col- CD22, anti-CD27, anti-IgM, anti-IgD and anti- 3 CD38 monoclonal antibodies. itis , and experimental mouse models suggest Results: Circulating IgM memory B cells were a protective role of B cells in chronic colitis4,5. significantly lower in Crohn’s disease (median In human peripheral blood, B cell subsets 7.1%, range 1.8-20.7) and ulcerative colitis pa- can be identified using surface markers such tients (median 8.1%, range 2.1-18.8) in compari- as CD22, CD24 and CD27. The latter dis- son to control subjects (median 14.0%, range - 6.8-31.1). As expected, there was a highly signifi- criminates peripheral naïve (CD27 ) from cant difference in the proportion of IgM memory memory (CD27+) B cells6. Memory B cells B cells between splenectomized patients (medi- represent 30-60% of the B cell pool7 and can an 2.4%, range 0.9-6.9) and healthy controls. be subdivided in IgM memory and switched Crohn’s disease patients with abscesses showed memory. IgM memory B cells differ from the lowest frequency of IgM memory B cells. Discussion: Our findings show that peripheral switched because they express IgM and their IgM memory B cells are reduced in inflammatory frequency may vary from 20-50% of the total bowel disease patients. Further studies are nec- memory pool. Switched memory express IgG, essary to answer the question of whether high IgA or IgE and lack surface expression of risk of infection (abscess development) is pro- IgM and IgD8. It has recently been shown moted by the reduction/depletion of IgM memory B-cell pool in inflammatory bowel disease. that these two cell subsets have different ori- gins and functions. Switched memory B cells, Key Words: which are only transiently depleted after Crohn’s disease, IgM memory B cell, Ulcerative colitis. splenectomy and are present at normal fre- quency in asplenic patients, derive from the 199 A. Di Sabatino, R. Carsetti, M.M. Rosado, R. Ciccocioppo, P. Cazzola, et al. germinal centres, whereas IgM memory B patients had had an elective procedure for cells, which are involved in the immune re- staging of Hodgkin’s disease (4 cases), or sponse to encapsulated bacteria, are re- non-malignant disease, such as hypersplenism duced/undetectable in splenectomized pa- due to cirrhosis (1 case), immune thrombocy- tients and thus require the spleen for their topenia (1 case), splenic artery aneurism (1 survival and/or generation9,10. case) and splenic cysts (1 case). As it is known that infections are one of Each subject gave informed consent to the the most frequent comorbid conditions in in- study. flammatory bowel disease11, the aim of our study was to verify whether in Crohn’s dis- Flow Cytometric Analysis ease and ulcerative colitis patients the IgM Peripheral blood mononuclear cells memory B cells pools was decreased. isolated from heparinized peripheral blood by Lymphoprep gradient centrifugation (Nicamed, Oslo, Norway) were stained with the appropriate antibody combinations of flu- Patients and Methods orescein, phycoerythrin, APC, cychrome, or biotin-labelled antibodies followed by strep- Patients tavidin-cychrome and streptavidin-APC Peripheral blood samples were obtained (Caltag Laboratories Inc., Burlingame, CA), from 22 patients with Crohn’s disease (mean as previously described9. Monoclonal anti- age 36.1, range 24-69), 20 patients with ulcera- bodies HIB19 (anti-CD19), HIB22 (anti- tive colitis (mean age 38.2 yrs, range 20-68), 22 CD22), M-T271 (anti-CD27), G20-127 (anti- healthy controls (mean age 38.3 yrs, range 22- IgM), IA6-2 (anti-IgD) and HIT2 (anti- 68) and 18 splenectomized patients (mean age CD38) were obtained from BD Biosciences 40.3 yrs, range 24-69). Diagnosis of Crohn’s (San Jose, CA) and anti-IgM Fc5µ fragment disease and ulcerative colitis was established specific was obtained from Jackson Immuno- according to the usual clinical criteria, and the Research Laboratories, Inc. (West Grove, site and extent of the disease were confirmed PA). Dead cells were excluded from analysis by endoscopy and histology in all patients. by side/forward scatter gating. All analyses Disease activity in Crohn’s disease patients were performed on a FACSCalibur (Becton was assessed by Crohn’s disease activity index Dickinson Co.) interfaced to a Macintosh (CDAI). Patients with scores below 150 were CellQuestTM computer program. classified as being in remission, whereas those with scores over 450 had severe disease12. Statistical Analysis Disease activity in ulcerative colitis patients Data were analyzed in the GraphPad was assessed according to the clinical activity Prism statistical PC program (GraphPad index (CAI) of Rachmilewitz13. Clinical remis- Software, San Diego, CA) by means of the sion was defined as a CAI score below 6. non-parametric Mann-Whitney U-test. A lev- Among the 22 Crohn’s disease patients, 10 el of p < 0.05 was considered statistically sig- were untreated at the time of inclusion in the nificant. study, 8 were treated with mesalazine and two with antibiotics and had suspended the treat- ment with steroids or other immunosuppressive agents at least three months earlier, two were Results treated with steroids. Among the 20 ulcerative colitis patients, 10 were untreated, 8 were treat- Mature and memory B cells can be identi- ed with mesalazine and had suspended the fied using a combination of the B cell marker treatment with steroids or other immunosup- CD2214 and CD27, which is expressed on pressive agents at least three months before the memory B cells6. Based on the relative ex- analysis and two were treated with steroids. pression of IgM and IgD, memory B cells We also analysed 18 splenectomized pa- were subdivided into IgM memory (IgMbright tients. In 10 individuals splenectomy was per- IgDdull) and switched memory B cells (IgM- formed after traumatic rupture of the spleen IgD-). Figure 1 shows the frequency of B cells caused by external injury. The remaining 8 and the distribution of their subsets in all pa- 200 Immunoglobulin M memory B cell decrease in inflammatory bowel disease B cells Memory B cells p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 % of total B cells IgM memory B cells Switched memory B cells p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 % of total B cells % of total lymphocytes % of total B cells Figure 1. Frequency of B cells, calculated as percentage of total lymphocytes, and frequency of memory, IgM mem- ory and switched memory B cells, calculated as a percentage of total B cells, in 18 splenectomized patients (SP), 22 Crohn’s disease patients (CD), 20 ulcerative colitis patients (UC) and 22 healthy controls (HC). tients and controls. The frequency of circulat- tients who had abscesses showed the lowest ing memory B cells was significantly lower in frequency of IgM memory B cells. Unlike Crohn’s disease (median 18.0%, range 4.1- IgM memory, switched memory B cells did 31.4) and ulcerative colitis patients (median not significantly differ in splenectomized pa- 18.9%, range 6.1-40.9) than in controls (medi- tients (median 13.1%, range 2.2-24.6), an 29.8%, range 21.1-44.2), although it re- Crohn’s disease (median 12.3%, range 2.8- mained significantly higher than in splenec- 30.2), ulcerative colitis (median 13.7%, range tomized patients (median 9.5%, range 3.7- 4.6-27.5) and the control group (median 18.7). There was no significant difference in 13.4%, range 6.0-24.7). The percentages of the frequency of memory B cells between ul- circulating memory, IgM memory and cerative colitis and Crohn’s disease patients. switched memory B cells did not correlate Further analysis demonstrated that only with disease activity and duration, either in IgM memory B cells were significantly lower Crohn’s disease or ulcerative colitis.
Load more

Recommended publications
  • Defining Natural Antibodies
    PERSPECTIVE published: 26 July 2017 doi: 10.3389/fimmu.2017.00872 Defining Natural Antibodies Nichol E. Holodick1*, Nely Rodríguez-Zhurbenko2 and Ana María Hernández2* 1 Department of Biomedical Sciences, Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United States, 2 Natural Antibodies Group, Tumor Immunology Division, Center of Molecular Immunology, Havana, Cuba The traditional definition of natural antibodies (NAbs) states that these antibodies are present prior to the body encountering cognate antigen, providing a first line of defense against infection thereby, allowing time for a specific antibody response to be mounted. The literature has a seemingly common definition of NAbs; however, as our knowledge of antibodies and B cells is refined, re-evaluation of the common definition of NAbs may be required. Defining NAbs becomes important as the function of NAb production is used to define B cell subsets (1) and as these important molecules are shown to play numerous roles in the immune system (Figure 1). Herein, we aim to briefly summarize our current knowledge of NAbs in the context of initiating a discussion within the field of how such an important and multifaceted group of molecules should be defined. Edited by: Keywords: natural antibody, antibodies, natural antibody repertoire, B-1 cells, B cell subsets, B cells Harry W. Schroeder, University of Alabama at Birmingham, United States NATURAL ANTIBODY (NAb) PRODUCING CELLS Reviewed by: Andre M. Vale, Both murine and human NAbs have been discussed in detail since the late 1960s (2, 3); however, Federal University of Rio cells producing NAbs were not identified until 1983 in the murine system (4, 5).
    [Show full text]
  • Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response
    Journal of Patient-Centered Research and Reviews Volume 4 Issue 3 Article 5 8-10-2017 Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response Michael A. Thompson Martin K. Oaks Maharaj Singh Karen M. Michel Michael P. Mullane Husam S. Tarawneh Angi Kraut Kayla J. Hamm Follow this and additional works at: https://aurora.org/jpcrr Part of the Immune System Diseases Commons, Medical Immunology Commons, Neoplasms Commons, Oncology Commons, Public Health Education and Promotion Commons, and the Respiratory Tract Diseases Commons Recommended Citation Thompson MA, Oaks MK, Singh M, Michel KM, Mullane MP, Tarawneh HS, Kraut A, Hamm KJ. Multiple myeloma baseline immunoglobulin G level and pneumococcal vaccination antibody response. J Patient Cent Res Rev. 2017;4:131-5. doi: 10.17294/2330-0698.1453 Published quarterly by Midwest-based health system Advocate Aurora Health and indexed in PubMed Central, the Journal of Patient-Centered Research and Reviews (JPCRR) is an open access, peer-reviewed medical journal focused on disseminating scholarly works devoted to improving patient-centered care practices, health outcomes, and the patient experience. BRIEF REPORT Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response Michael A. Thompson, MD, PhD,1,3 Martin K. Oaks, PhD,2 Maharaj Singh, PhD,1 Karen M. Michel, BS,1 Michael P. Mullane,3 MD, Husam S. Tarawneh, MD,3 Angi Kraut, RN, BSN, OCN,1 Kayla J. Hamm, BSN3 1Aurora Research Institute, Aurora Health Care, Milwaukee, WI; 2Transplant Research Laboratory, Aurora St. Luke’s Medical Center, Aurora Health Care, Milwaukee, WI; 3Aurora Cancer Care, Aurora Health Care, Milwaukee, WI Abstract Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system.
    [Show full text]
  • Selective Igm Immunodeficiency: Retrospective Analysis of 36 Adult Patients with Review of the Literature Marc F
    Review Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature Marc F. Goldstein, MD*; Alex L. Goldstein, BS†; Eliot H. Dunsky, MD*; Donald J. Dvorin, MD*; George A. Belecanech, MD*; and Kfir Shamir, MD‡ Objective: To review and compare previously reported cases of selective IgM immunodeficiency (SIgMID) with the largest adult cohort obtained from a retrospective analysis of an allergy and immunology practice. Data Sources: Publications were selected from the English-only PubMed database (1966–2005) using the following keywords: IgM immunodeficiency alone and in combination with celiac disease, autoimmune disease, malignancy, and infection. Bibliographic references of relevant articles were used. Study Selection: Reported adult SIgMID cases were reviewed and included in a comparative database against our cohort. Results: Previously described patients with SIgMID include 155 adults and 157 patients of unspecified age. Thirty-six adult patients were identified with SIgMID from a database of 13,700 active adult patients (0.26%, 1:385). The mean Ϯ SD serum IgM level was 29.74 Ϯ 8.68 mg/dL (1 SD). The mean Ϯ SD age at the time of diagnosis of SIgMID was 55 Ϯ 13.5 years. Frequency of presenting symptoms included the following: recurrent upper respiratory tract infections, 77%; asthma, 47%; allergic rhinitis, 36%; vasomotor rhinitis, 19%; angioedema, 14%; and anaphylaxis, 11%. Serologically, 13% of patients had positive antinuclear antibodies (ANAs), 5% had serologic evidence of celiac disease, and nearly all had non-AB blood type. Patients also had low levels of IgM isohemagglutinins. No patients developed lymphoproliferative disease or panhypogammaglobulinemia, and none died of life-threat- ening infections, malignancy, or fulminant autoimmune-mediated diseases during a mean follow-up period of 3.7 years.
    [Show full text]
  • Structure, Function, and Therapeutic Use of Igm Antibodies
    antibodies Review Structure, Function, and Therapeutic Use of IgM Antibodies Bruce A. Keyt *, Ramesh Baliga, Angus M. Sinclair, Stephen F. Carroll and Marvin S. Peterson IGM Biosciences Inc, 325 East Middlefield Road, Mountain View, CA 94043, USA; [email protected] (R.B.); [email protected] (A.M.S.); [email protected] (S.F.C.); [email protected] (M.S.P.) * Correspondence: [email protected]; Tel.: +1-650-265-6458 Received: 16 September 2020; Accepted: 9 October 2020; Published: 13 October 2020 Abstract: Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro- immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract.
    [Show full text]
  • Selective Igm Deficiency—An Underestimated Primary Immunodeficiency
    UC Irvine UC Irvine Previously Published Works Title Selective IgM Deficiency-An Underestimated Primary Immunodeficiency. Permalink https://escholarship.org/uc/item/6wg240n5 Journal Frontiers in immunology, 8(SEP) ISSN 1664-3224 Authors Gupta, Sudhir Gupta, Ankmalika Publication Date 2017 DOI 10.3389/fimmu.2017.01056 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW published: 05 September 2017 doi: 10.3389/fimmu.2017.01056 Selective IgM Deficiency—An Underestimated Primary Immunodeficiency Sudhir Gupta* and Ankmalika Gupta† Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, United States Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number Edited by: of B cell subset abnormalities have been reported and impaired specific antibodies Guzide Aksu, to Streptococcus pneumoniae responses are observed in more than 45% of cases. Ege University, Turkey Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. Reviewed by: Amos Etzioni, The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM University of Haifa, Israel are also unable to control infections from bacterial, viral, and fungal pathogens, and Isabelle Meyts, develop autoimmunity.
    [Show full text]
  • Immunoglobulin M 1E01-20 30-3962/R3
    IMMUNOGLOBULIN M 1E01-20 30-3962/R3 IMMUNOGLOBULIN M This package insert contains information to run the Immunoglobulin M assay on the ARCHITECT c Systems and the AEROSET System. NOTE: Changes Highlighted NOTE: This package insert must be read carefully prior to product use. Package insert instructions must be followed accordingly. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. Customer Support United States: 1-877-4ABBOTT Canada: 1-800-387-8378 (English speaking customers) 1-800-465-2675 (French speaking customers) International: Call your local Abbott representative Symbols in Product Labeling Calibrators 1 through 5 Catalog number/List number Concentration Serial number Authorized Representative in the Consult instructions for use European Community Ingredients Manufacturer In vitro diagnostic medical device Temperature limitation Batch code/Lot number Use by/Expiration date Reagent 1 Reagent 2 December 2009 ©2004, 2009 Abbott Laboratories 1 NAME REAGENT HANDLING AND STORAGE (Continued) IMMUNOGLOBULIN M Reagent Storage Unopened reagents are stable until the expiration date when stored INTENDED USE at 2 to 8°C. The Immunoglobulin M (IgM) assay is used for the quantitation of IgM in Reagent onboard stability is approximately 57 days if quality control human serum or plasma. results meet acceptance criteria. If quality control results do not meet acceptance criteria, refer to the QUALITY CONTROL section of this SUMMARY AND EXPLANATION OF TEST package insert. IgM, primarily present as a pentamer, is the first immunoglobulin class produced during an initial immune response and antigen-IgM complexes WARNINGS AND PRECAUTIONS actively fix complement.
    [Show full text]
  • CASE REPORT a Case of Multiple Myeloma with Unusual Serum
    Introduction segments during the performance of activities. Acquired brain injuries, such as Thus, the rehabilitation of children with mild hypoxic-ischemic lesions up to the age of three, motor impairment of the hemiplegic type may are among the ten main causes of spastic prove to be especially challenging to therapists, hemiplegic cerebral palsy (CP). Although it requiring profound technical knowledge and does not severely impair functionality in creativity. children, hemiplegic motor impairment The progression of the therapy in these children produces neuromotor alterations that cause is often compromised by the difficulty in finding precision deficits in movement performance and tasks that motivate them, while at the same time deficits in postural control, which is responsible showing therapeutic efficacy. for the stability and alignment between the body Developmental therapy allows the child with and nervous system are maturing in the presence the human nervous system when damaged has of the damage and this cannot take place in a powers of compensation. In addition, the baby vacuum. The way the baby is handled and the and young child are still maturing and dormant mild motor impairment and high levels of temporal, posterior temporal and occipital attitudes that surround the baby influence how abilities can be activated. In cerebral palsy there functionality to perform tasks close to those regions. MRI of brain was advised. the maturation expresses itself in the subsequent is a potential for abnormal patterns of movement performed in their daily routine, facilitating the Developmental Therapy (motor therapy, child’s and adult’s ultimate function. and posture to become habitual and deformities transposition of the motor learning generated stimulation program, visual stimulation) is Although the motor delay and dysfunctions are can occur and become fixed.
    [Show full text]
  • Immunoglobulin M in the Cerebrospinal Fluid: an Indicator of Recent Immunological Stimulation
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.8.949 on 1 August 1989. Downloaded from Journal ofNeurology, Neurosurgery, and Psychiatry 1989;52:949-953 Immunoglobulin M in the cerebrospinal fluid: an indicator of recent immunological stimulation M K SHARIEF, E J THOMPSON From the Department ofClinical Neurochemistry, Institute ofNeurology, The National Hospitalfor Nervous Diseases, London SUMMARY Using a sensitive new method for detecting oligoclonal immunoglobulin M (IgM) in unconcentrated cerebrospinal fluid (CSF), the intrathecal synthesis of IgM was correlated with that of free light chains in patients with multiple sclerosis, infections of the central nervous system and other neurological conditions. A strong correlation was found between the presence of oligoclonal IgM and that offree light chains in the CSF from patients with multiple sclerosis and infections ofthe central nervous system. No oligoclonal IgM response was observed in patients with non-inflam- matory or non-infectious neurological conditions. This implies that oligoclonal IgM has the same diagnostic significance as free light chains. Electrophoretically restricted immunoglobulins (Ig) Despite the potential importance of CSF oligo- Protected by copyright. commonly occur in the cerebrospinal fluid (CSF) of clonal IgM, the pace of progress in this field has been patients with inflammatory and infectious diseases of hampered by methodological difficulties in detecting the central nervous system (CNS) in the form of the very low amounts of IgM that are usually present oligoclonal bands where each band represents the in CSF. We have applied a new sensitive method'" of product of a single B-lymphocyte clone. detecting qualitative alterations of CSF IgM to study Another immunological parameter is CSF free light the relationship between intrathecally synthesised chains.
    [Show full text]
  • CUTANEOUS IMMUNE COMPLEX VASCULITIS, SKIN-LIMITED CUTANEOUS IGA OR IGG/IGM VASCULITIS (Formerly Called: Allergic/Hypersensitivity Vasculitis)
    EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY Information Leaflet for Patients CUTANEOUS IMMUNE COMPLEX VASCULITIS, SKIN-LIMITED CUTANEOUS IGA OR IGG/IGM VASCULITIS (Formerly called: Allergic/Hypersensitivity Vasculitis) The aim of this leaflet This leaflet is designed to help you understand more about cutaneous immune complex vasculitis or skin -limited IgA or IgG/IgM vasculitis (formerly called allergic/hypersensitivity vasculitis). It tells you what this condition is, what causes it, and what can be done for treatment. CUTANEOUS What are immunoglobulins (IgA, IgG and IgM)? Immunoglobulins or antibodies are proteins made by the immune system to fight antigens, IMMUNE COMPLEX such as bacteria, viruses, and toxins. The body makes 5 different types of immunoglobulins VASCULITIS, to combat different antigens. Immunoglobulin A (IgA): is found in high concentrations in the mucous membranes, SKIN-LIMITED particularly those lining the respiratory passages and gastrointestinal tract, as well as in CUTANEOUS saliva and tears. Immunoglobulin G (IgG): the most abundant type of antibody, is found in all body fluids and IGA OR IGG/IGM protects against bacterial and viral infections. VASCULITIS Immunoglobulin M (IgM), which is found mainly in the blood and lymph fluid, is the first antibody to be made by the body to fight a new infection. What is allergic vasculitis? In half of cases, a trigger of cutaneous immune complex vasculitis can be identified, Cutaneous immune complex vasculitis, the most common of which include recent usually manifesting as skin -limited IgA or acute infections (eg. upper respiratory tract IgG/IgM vasculitis (formerly called:¨Allergic/ infections, viral hepatitis and HIV infection) hypersensitivity vasculitis) belongs to the or certain medications: antibiotics are cutaneous small-vessel vasculitides, and is a the most common drugs to cause disorder characterized by the inflammation cutaneous immune complex vasculitis, of some small blood vessels located mainly particularly beta-lactams.
    [Show full text]
  • Comprehensive Review of Autoantibodies in Patients with Hyper-Igm Syndrome
    Cellular and Molecular Immunology (2018) 15, 610–617 & 2018 CSI and USTC All rights reserved 2042-0226/18 $32.00 www.nature.com/cmi RESEARCH ARTICLE Comprehensive review of autoantibodies in patients with hyper-IgM syndrome Mohamed-Ridha Barbouche1, Qubo Chen2,3, Marco Carbone4, Imen Ben-Mustapha1, Zakera Shums5, Mehdi Trifa6, Federica Malinverno4, Francesca Bernuzzi4, Haiyan Zhang2,4,7, Nourhen Agrebi1, Gary L Norman5, Christopher Chang8, M Eric Gershwin8 and Pietro Invernizzi2,4 Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene. The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis. In the present study, we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome. Serum, liver-related and liver-not-related autoantibodies IgG, IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients (8 males and 5 females, aged 1–12 years) with hyper-immunoglobulin M syndrome during 1995–2012 and, as controls, 21 age- and gender-matched blood donors. The level of IgM antibody against MIT3 was significantly higher in patients than in controls (35.8 vs 10.7, P = 0.002). Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls (Po0.0001). Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05% of controls. By immunofluorescence, 92.3% of patients were MIT3 IgM positive vs none of the controls.
    [Show full text]
  • Understanding the Immune System and Lymphoma
    Understanding the Immune System and Lymphoma The body’s immune system is comprised of a network of cells, tissues, and organs. This network operates together to eliminate harmful pathogens, like bacteria and viruses, as well as cancer cells from the body. The immune system provides two different types of immunity: • Innate (meaning “inborn” or “natural”) immunity — This type of immunity is provided by natural barriers in the body, substances in the blood, and specific cells that attack and kill foreign cells. Examples of natural barriers include skin,mucous membranes, stomach acid, and the cough reflex. These barriers keep germs (bacteria or viruses) and other harmful substances from entering the body. Inflammation (redness and swelling) is also a type of innate immunity. Blood cells that are part of the innate immune system include neutrophils, macrophages, eosinophils, and basophils. • Adaptive (meaning adapting to external forces or threats) immunity — This type of immunity is provided by the thymus gland, spleen, tonsils, bone marrow, circulatory system, and lymphatic system. B cells and T cells, the two main types of lymphocytes, carry out the adaptive immune response by recognizing and either inactivating or killing specific invading organisms. The adaptive immune system can then “remember” the identity of the invader, so that the next time the body is infected by the same invader, the immune response will develop more quickly and strongly. All normal cells have a limited lifespan. A self-destruct mechanism called apoptosis is triggered when cells become senescent (too old) or get damaged; this natural process is called apoptosis or programmed sequence of events that lead to the cell’s death.
    [Show full text]
  • Igm Antigen Receptor Complex Contains Phosphoprotein Products of B29 and Mb-I Genes (Membrane Immunoglobulin/B Lymphocyte/Signal Transduction) KERRY S
    Proc. Natl. Acad. Sci. USA Vol. 88, pp. 3982-3986, May 1991 Immunology IgM antigen receptor complex contains phosphoprotein products of B29 and mb-i genes (membrane immunoglobulin/B lymphocyte/signal transduction) KERRY S. CAMPBELL*, ELIZABETH J. HAGER*, R. JOACHIM FRIEDRICH*, AND JOHN C. CAMBIER*tt *National Jewish Center for Immunology and Respiratory Medicine, Division of Basic Research, Department of Pediatrics, Denver, CO 80206; and tUniversity of Colorado Health Sciences Center, Department of Microbiology and Immunology, Denver, CO 80206 Communicated by Philippa Marrack, February 20, 1991 ABSTRACT Membrane immunoglobulin M (mIgM) and (32 kDa), Ig-,B (37 kDa), and Ig-y(34 kDa) (13, 14). All ofthese mIgD are major B-lymphocyte antigen receptors, which func- components are inducibly phosphorylated on tyrosine resi- tion by internalizing antigens for processing and presentation dues upon receptor ligation or treatment of cells with alumi- to T cells and by transducing essential signals for proliferation num fluoride (ref. 13 and K.S.C. and J.C.C., unpublished and differentiation. Although ligation ofmIgM or mIgD results observations). IgM-a is found disulfide-linked as a het- in rapid activation of a phospholipase C and a tyrosine ki- erodimer with either Ig-P or Ig-y (13, 14). nase(s), these receptors have cytoplasmic tails of only three Studies by Reth and colleagues (11, 12) have provided amino acid residues (Lys-Val-Lys), which seem ill suited for evidence that expression of the mb-i gene product, MB-1, is direct physical coupling with cytoplasmic signal transduction crucial for mIgM surface expression. Concurrently, they structures.
    [Show full text]