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Interpretation of Autoantibodies in Rheumatological Diseasesଝ Document downloaded from http://www.elsevier.es, day 26/02/2019. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. r e v c o l o m b r e u m a t o l . 2 0 1 8;2 5(2):112–125 w ww.elsevier.es/rcreuma Review article Interpretation of autoantibodies in rheumatological diseasesଝ a a b c Tatiana Mendez-Rayo , Laura Ochoa-Zárate , Iván Posso-Osorio , Eliana Ortiz , b b,c,∗ Juan Naranjo-Escobar , Gabriel J. Tobón a Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia b GIRAT: Grupo de Investigación en Reumatología, Autoinmunidad y Medicina Traslacional, Fundación Valle del Lili y Universidad Icesi, Cali, Colombia c Laboratorio de Inmunología, Fundación Valle del Lili, Cali, Colombia a r t i c l e i n f o a b s t r a c t Article history: Autoimmune diseases are a group of chronic diseases in which genetic, environmental, Received 23 November 2017 and hormonal factors contribute to their appearance. In addition to having a broad clini- Accepted 26 February 2018 cal spectrum, the interpretation of the various autoantibodies and techniques used in the laboratory is also a clinical challenge. Given the complexity of these diseases, it is very important to rely on the results of laboratory tests to establish a correct diagnosis and Keywords: follow-up and, in some cases even to establish a prognosis or prediction of autoimmu- Autoimmunity nity. Taking all this into account, it is intended to improve the quality of life of patients Autoantibodies by decreasing the increased morbidity and mortality in this group of diseases, especially Systemic lupus erythematosus by early diagnosis. Most rheumatological diseases are characterized by the high production Rheumatoid arthritis of autoantibodies and acute phase reactants, which are involved in their pathophysiology, Sjögren’s syndrome leading to systemic involvement. Among these, the most recognized are, systemic lupus ery- Indirect immunofluorescence thematosus, rheumatoid arthritis, and Sjögren’s syndrome. For these reasons, the objective technique of this project is to present a review that will help both physicians and laboratory personnel Enzyme-linked immunosorbent in the interpretation of the different autoantibodies in autoimmune diseases. assay © 2018 Asociacion´ Colombiana de Reumatologıa.´ Published by Elsevier Espana,˜ S.L.U. All Antinuclear antibodies rights reserved. Rheumatoid factor Anti-cyclic citrullinated peptide PII of original article: S0121-8123(18)30029-X ଝ Please cite this article as: Mendez-Rayo T, Ochoa-Zárate L, Posso-Osorio I, Ortiz E, Naranjo-Escobar J, Tobón GJ. Interpretación de los autoanticuerpos en enfermedades reumatológicas. Rev Colomb Reumatol. 2018;25:112–125. ∗ Corresponding author. E-mail address: [email protected] (G.J. Tobón). 2444-4405/© 2018 Asociacion´ Colombiana de Reumatologıa.´ Published by Elsevier Espana,˜ S.L.U. All rights reserved. Document downloaded from http://www.elsevier.es, day 26/02/2019. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. r e v c o l o m b r e u m a t o l . 2 0 1 8;2 5(2):112–125 113 Interpretación de los autoanticuerpos en enfermedades reumatológicas r e s u m e n Las enfermedades autoinmunes son un grupo de patologías crónicas en las que fac- Palabras clave: Autoinmunidad tores genéticos, ambientales y hormonales, contribuyen a su aparición. Además de tener Autoanticuerpos un amplio espectro clínico, la interpretación de los diversos autoanticuerpos y técnicas Lupus Eritematoso Sistémico utilizadas en el laboratorio también son un reto clínico. Dada la complejidad de estas enfer- Artritis Reumatoide medades, es muy importante apoyarse en las pruebas de laboratorio para establecer un Síndrome de Sjögren correcto diagnóstico, seguimiento y, en algunos casos inclusive, establecer pronósticos o Inmunofluorescencia indirecta predicción de la posible aparición de autoinmunidad. Con todo esto, se pretende mejo- Enzimoinmunoanálisis rar la calidad de vida de los pacientes disminuyendo la gran morbimortalidad de este Anticuerpos Antinucleares grupo de patologías, especialmente al diagnosticarlas en etapas tempranas. La mayoría de Factor Reumatoide enfermedades reumatológicas se caracterizan por la alta producción de autoanticuerpos y Anticuerpos Antipéptidos reactantes de fase aguda, los cuales estas implicados en su fisiopatología produciendo dano˜ cíclicos citrulinados directo a nivel sistémico. Entre estas, el Lupus Eritematoso Sistémico, la Artritis Reumatoide y el Síndrome de Sjögren son las más reconocidas. Por tales motivos, el objetivo de este tra- bajo es hacer una revisión que permita guiar tanto a médicos como personal de laboratorio en la interpretación de los diferentes autoanticuerpos en enfermedades autoinmunes. © 2018 Asociacion´ Colombiana de Reumatologıa.´ Publicado por Elsevier Espana,˜ S.L.U. Todos los derechos reservados. Introduction Methods Autoimmune diseases are a complex and heterogeneous Literature search methods group of pathologies, which are the result of the interaction between genetic, epigenetic, immunological and environmen- A systematic literature search was conducted from June 2017 tal factors. About 5% of the world population is affected by to October 2017, including articles published from 1970 until 1 organ-specific and systemic autoimmune diseases. It has 2017. Different online databases such as Medline, Google been raised that there are different phases before the autoim- Scholar, Scielo, Clinical Trials, Academic Search Ultimate, Clin- mune disease occurs and the investigation on these phases ics Review Article and Embase were consulted. The search points to a future where primary prevention that can delay in Pubmed was carried out using the MeSH terms: Autoin- or postpone the onset of the disease can be performed, based munidad, Autoanticuerpos, Lupus eritematoso sistémico, Artritis on models of predictability founded on the determination of reumatoide, Síndrome de Sjögren, Inmunofluorescencia indirecta, 1,2 autoantibodies. This is how it is considered that the appear- Enzimoinmunoanálisis (Autoimmunity, Autoantibodies, Sys- ance of autoantibodies has an important role in the evolution temic lupus erythematosus, Rheumatoid arthritis Sjögren’s toward the clinical presentation of different autoimmune dis- syndrome, Indirect immunofluorescence, Enzyme Immunoas- eases. say). These terms were linked with the Boolean connector The autoantibodies found in autoimmune diseases are the AND. Those articles published before 1970 were excluded, result of errors in the regulatory mechanisms or of a consid- and only articles published in English or Spanish were erable increase in the self-antigens due to alteration in the included. regulatory mechanisms. Within the wide range of autoanti- bodies that have been studied, the vast majority of those that we determine in clinical practice have an important role as Selection of articles and information extraction markers of autoimmunity and diagnosis in a specific clinical The selected articles were stored in an electronic database; context. On the contrary, within this group of tests, very few initially, those articles that had the keywords included in the are indicators of disease activity (for example, anti-double- 3 abstract or in the title were taken into account. Subsequently, stranded DNA antibodies in systemic lupus) and pathogenic. those articles which did not meet the inclusion criteria or In this article we will describe the most important and com- the methodological quality were discarded, and a committee monly used antibodies in the clinical context, highlighting among the different authors was held in order to unify the the most relevant characteristics and the role they play in database and choose those articles that were relevant for this the diagnosis, prediction, follow-up and prognosis of different publication. autoimmune diseases. Document downloaded from http://www.elsevier.es, day 26/02/2019. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. 114 r e v c o l o m b r e u m a t o l . 2 0 1 8;2 5(2):112–125 Inclusion criteria The method used for the identification of the ANAs in HEp-2 cells is, by convention, the indirect immunofluores- 1. Types of study: Topic reviews, case-control, randomized cence (IIF), although new techniques for the detection of these and non-randomized studies, cohort studies, case reports antibodies have been developed currently, the former is still 7 and institutional protocols. considered the gold standard. IIF is a method accessible 2. Type of population: Adult healthy patients and with in many laboratories and easy to reproduce. For this test is autoimmunity. required the serum of the patient, which is initially diluted in 3. Intervention: Studies describing history, laboratory tech- 1/40 or more, and then is added to the preparation of HEp-2 niques, applicability and clinical function of the antibodies. cells, thus allowing the patient’s antibodies to bind with the target antigens present in these cells. A wash is carried out Exclusion criteria then with a buffer solution, and subsequently, a solution with anti-human IgG coupled to a fluorochrome that binds to the 1. Articles without access to the full text. antigen/antibody complex present in the sample is applied. 2. Duplicate articles. Finally, after a second wash that removes the fluorescent anti- 3. Studies that were not conducted in humans. bodies that did not bind, the result can be observed by means 4. Articles published before 1970. of an ultraviolet light microscope. HEp-2 cells are ideal for this type of test, since they are easy to grow and they grow forming a monolayer, which allows their visualization through the flu- Results orescence microscope. In addition, they have a bigger nucleus than the one of any normal epithelial cell, which makes eas- At the end of the search, a total of 124 articles were found by ier the visualization of the nuclear and cytoplasmic patterns. all researchers. Excluding those duplicate or without access, Moreover, these cells allow to detect antibodies against cell a total of 77 articles were obtained.
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