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      Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

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          Abstract

          The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.

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          A 52-kD protein is a novel component of the SS-A/Ro antigenic particle

          Anti-SS-A/Ro autoantibodies are found in the sera of patients with Sjogren's syndrome (SS) and SLE. In the course of analyzing 61 SS patients for their autoantibody profiles, we found that 42 were positive for anti-SS-A by double diffusion in agarose and demonstrated precipitin lines identical to that produced by a prototype anti-SS-A serum. Further analysis of these SS-A antibody-positive sera by Western blotting of cell extracts revealed that 21 sera reacted with two proteins of 60 and 52 kD, 13 sera reacted with 52-kD protein, two detected only 60 kD, while six were nonreactive. Affinity-purified anti- 60-kD and anti-52-kD antibodies reacted exclusively with their corresponding antigens. Partial proteolysis of these proteins did not reveal common degradation fragments. Thus the 52- and 60-kD proteins were found to be antigenically and apparently structurally distinct from each other. They were also distinct from 48-kD SS-B/La protein. In immunoprecipitation using labeled cell extracts, affinity-purified anti- 52-kD antibodies brought down the 52-kD protein as well as the 60-kD band. In [32P]orthophosphate-labeled HeLa cell extract both antibodies precipitated the same spectrum of small RNAs (hYl-5). In indirect immunofluorescence, anti-52-kD and anti-60-kD antibodies immunolocalized in similar subcellular structures and showed similar punctate nuclear staining patterns. Western blot analysis revealed that both proteins were present in lymphocytic as well as epithelial human cell lines tested. The data above define a new antigen of 52 kD which is another component of the SS-A particle and is associated in complex formation with the previously reported 60-kD protein.
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            Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis

            Introduction Autoantibodies to Ro52 recently identified as TRIM21 are among the most common autoantibodies in systemic autoimmune rheumatic diseases, but their clinical association remains poorly understood. We undertook this study to determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies in patients with systemic sclerosis (SSc). Methods Detailed clinical data and sera from 963 patients with SSc enrolled in a multicenter cohort study were collected and entered into a central database. Antibodies to Ro52/TRIM21 and other autoantibodies were detected with an addressable laser-bead immunoassay and different enzyme-linked immunosorbent assay (ELISA) systems. Associations between anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of SSc were investigated. Results Anti-Ro52/TRIM21 antibodies were present in 20% of SSc patients and overlapped with other main SSc-related antibodies, including anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P = 0.0059). Conclusions Anti-Ro52/TRIM21 antibodies were the second most common autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a marker of interstitial lung disease and overlap syndrome.
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              Clinical and laboratory aspects of Ro/SSA-52 autoantibodies.

              Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Int J Rheumatol
                Int J Rheumatol
                IJR
                International Journal of Rheumatology
                Hindawi Publishing Corporation
                1687-9260
                1687-9279
                2017
                22 January 2017
                : 2017
                : 3076017
                Affiliations
                1Biochemistry Unit, Central Laboratory, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain
                2Immunology Unit, Central Laboratory, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain
                3Rheumatology Department, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain
                Author notes

                Academic Editor: Charles J. Malemud

                Author information
                http://orcid.org/0000-0001-9981-4714
                http://orcid.org/0000-0002-4204-1236
                http://orcid.org/0000-0002-7560-1682
                http://orcid.org/0000-0002-6994-2034
                Article
                10.1155/2017/3076017
                5292168
                28210273
                eeb5dfbc-8151-45c4-9436-496bd218a614
                Copyright © 2017 Ana Alonso-Larruga et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 November 2016
                : 29 December 2016
                Categories
                Research Article

                Rheumatology
                Rheumatology

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