Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis
Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed...
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doaj-689d410b2463459db1f73c5bde547c482020-11-24T22:17:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02835406940Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic SclerosisAthanasios Gkoutzourelas0Christos Liaskos1Maria G. Mytilinaiou2Theodora Simopoulou3Christina Katsiari4Alexandra Tsirogianni5Dimitrios Daoussis6Thomas Scheper7Wolfgang Meyer8Dimitrios P. Bogdanos9Lazaros I. Sakkas10Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Immunology-Histocompatibility, Evangelismos General Hospital, Athens, GreeceDepartment of Rheumatology, Patras University Hospital, Faculty of Medicine, University of Patras Medical School, Patras, GreeceInstitute of Immunology Affiliated to Euroimmun AG, Lübeck, GermanyInstitute of Immunology Affiliated to Euroimmun AG, Lübeck, GermanyDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceEpitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM), and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6 vs. 41.7%, p = 0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9 vs. 50%, p = 0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than in anti-Ro52+/anti-Ro60-patients (33.3 vs. 0%, p = 0.003). In this comprehensive analysis of Ro52 epitope mapping in SSc, the coiled coil domain remains the predominant epitope on Ro52. Contrary to SjS and SLE, patients with SSc fail to identify epitopic regions within the N-terminus of the protein, especially if they lack con-current anti-Ro60 reactivity.https://www.frontiersin.org/article/10.3389/fimmu.2018.02835/fullautoantibodyautoimmunityautoimmune rheumatic diseasesepitopeSS-A |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Athanasios Gkoutzourelas Christos Liaskos Maria G. Mytilinaiou Theodora Simopoulou Christina Katsiari Alexandra Tsirogianni Dimitrios Daoussis Thomas Scheper Wolfgang Meyer Dimitrios P. Bogdanos Lazaros I. Sakkas |
spellingShingle |
Athanasios Gkoutzourelas Christos Liaskos Maria G. Mytilinaiou Theodora Simopoulou Christina Katsiari Alexandra Tsirogianni Dimitrios Daoussis Thomas Scheper Wolfgang Meyer Dimitrios P. Bogdanos Lazaros I. Sakkas Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis Frontiers in Immunology autoantibody autoimmunity autoimmune rheumatic diseases epitope SS-A |
author_facet |
Athanasios Gkoutzourelas Christos Liaskos Maria G. Mytilinaiou Theodora Simopoulou Christina Katsiari Alexandra Tsirogianni Dimitrios Daoussis Thomas Scheper Wolfgang Meyer Dimitrios P. Bogdanos Lazaros I. Sakkas |
author_sort |
Athanasios Gkoutzourelas |
title |
Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis |
title_short |
Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis |
title_full |
Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis |
title_fullStr |
Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis |
title_full_unstemmed |
Anti-Ro60 Seropositivity Determines Anti-Ro52 Epitope Mapping in Patients With Systemic Sclerosis |
title_sort |
anti-ro60 seropositivity determines anti-ro52 epitope mapping in patients with systemic sclerosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-12-01 |
description |
Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM), and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6 vs. 41.7%, p = 0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9 vs. 50%, p = 0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than in anti-Ro52+/anti-Ro60-patients (33.3 vs. 0%, p = 0.003). In this comprehensive analysis of Ro52 epitope mapping in SSc, the coiled coil domain remains the predominant epitope on Ro52. Contrary to SjS and SLE, patients with SSc fail to identify epitopic regions within the N-terminus of the protein, especially if they lack con-current anti-Ro60 reactivity. |
topic |
autoantibody autoimmunity autoimmune rheumatic diseases epitope SS-A |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02835/full |
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