Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients

IntroductionSerum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren’s syndrome (SS). Most patients' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients di...

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Main Authors: Adrian Y. S. Lee, Trishni Putty, Ming-Wei Lin, Sanjay Swaminathan, Dan Suan, Tim Chataway, Rogier M. Thurlings, Tom P. Gordon, Jing Jing Wang, Joanne H. Reed
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115548/full
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author Adrian Y. S. Lee
Adrian Y. S. Lee
Trishni Putty
Trishni Putty
Ming-Wei Lin
Ming-Wei Lin
Sanjay Swaminathan
Sanjay Swaminathan
Dan Suan
Dan Suan
Tim Chataway
Rogier M. Thurlings
Tom P. Gordon
Tom P. Gordon
Jing Jing Wang
Jing Jing Wang
Joanne H. Reed
author_facet Adrian Y. S. Lee
Adrian Y. S. Lee
Trishni Putty
Trishni Putty
Ming-Wei Lin
Ming-Wei Lin
Sanjay Swaminathan
Sanjay Swaminathan
Dan Suan
Dan Suan
Tim Chataway
Rogier M. Thurlings
Tom P. Gordon
Tom P. Gordon
Jing Jing Wang
Jing Jing Wang
Joanne H. Reed
author_sort Adrian Y. S. Lee
collection DOAJ
description IntroductionSerum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren’s syndrome (SS). Most patients' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients diagnosed with SS with anti-Ro52 in the presence or absence of anti-Ro60/La autoantibodies.MethodsA cross-sectional study was performed. Patients in the SS biobank at Westmead Hospital (Sydney, Australia) that were positive for anti-Ro52 were included and stratified based on the absence (isolated) or presence (combined) of anti-Ro60/La, measured by line immunoassay. We examined clinical associations and the serological and molecular characteristics of anti-Ro52 using ELISA and mass spectrometry in serological groups.ResultsA total of 123 SS patients were included for study. SS patients with isolated anti-Ro52 (12%) identified a severe serological subset characterised by higher disease activity, vasculitis, pulmonary involvement, rheumatoid factor (RhF) and cryoglobulinaemia. Serum antibodies reacting with Ro52 in the isolated anti-Ro52 subset displayed less isotype switching, less immunoglobulin variable region subfamily usage and a lower degree of somatic hypermutation than the combined anti-Ro52 subset.ConclusionsIn our cohort of SS patients, isolated anti-Ro52 represents a severe subset of SS, and is associated with the presence of cryoglobulinaemia. We therefore provide clinical relevance to the stratification of SS patients by their sero-reactivities. It is possible that the autoantibody patterns may be immunological epiphenomena of the underlying disease process, and further work is required to unearth the mechanisms of the differential clinical phenotypes.
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spelling doaj.art-30337c3a00a4442cb3f1ee2d2e38b8392023-03-16T07:05:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11155481115548Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patientsAdrian Y. S. Lee0Adrian Y. S. Lee1Trishni Putty2Trishni Putty3Ming-Wei Lin4Ming-Wei Lin5Sanjay Swaminathan6Sanjay Swaminathan7Dan Suan8Dan Suan9Tim Chataway10Rogier M. Thurlings11Tom P. Gordon12Tom P. Gordon13Jing Jing Wang14Jing Jing Wang15Joanne H. Reed16Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, AustraliaDepartment of Clinical Immunology and Allergy, Westmead Hospital and Institute of Clinical Pathology & Medical Research (ICPMR), Westmead, NSW, AustraliaDepartment of Immunology, Flinders University, Bedford Park, SA, AustraliaDepartment of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, AustraliaCentre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, AustraliaDepartment of Clinical Immunology and Allergy, Westmead Hospital and Institute of Clinical Pathology & Medical Research (ICPMR), Westmead, NSW, AustraliaCentre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, AustraliaDepartment of Clinical Immunology and Allergy, Westmead Hospital and Institute of Clinical Pathology & Medical Research (ICPMR), Westmead, NSW, AustraliaCentre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, AustraliaDepartment of Clinical Immunology and Allergy, Westmead Hospital and Institute of Clinical Pathology & Medical Research (ICPMR), Westmead, NSW, AustraliaFlinders Proteomic Facility, Flinders University, Bedford Park, SA, AustraliaDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Immunology, Flinders University, Bedford Park, SA, AustraliaDepartment of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, AustraliaDepartment of Immunology, Flinders University, Bedford Park, SA, AustraliaDepartment of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, AustraliaCentre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, AustraliaIntroductionSerum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren’s syndrome (SS). Most patients' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients diagnosed with SS with anti-Ro52 in the presence or absence of anti-Ro60/La autoantibodies.MethodsA cross-sectional study was performed. Patients in the SS biobank at Westmead Hospital (Sydney, Australia) that were positive for anti-Ro52 were included and stratified based on the absence (isolated) or presence (combined) of anti-Ro60/La, measured by line immunoassay. We examined clinical associations and the serological and molecular characteristics of anti-Ro52 using ELISA and mass spectrometry in serological groups.ResultsA total of 123 SS patients were included for study. SS patients with isolated anti-Ro52 (12%) identified a severe serological subset characterised by higher disease activity, vasculitis, pulmonary involvement, rheumatoid factor (RhF) and cryoglobulinaemia. Serum antibodies reacting with Ro52 in the isolated anti-Ro52 subset displayed less isotype switching, less immunoglobulin variable region subfamily usage and a lower degree of somatic hypermutation than the combined anti-Ro52 subset.ConclusionsIn our cohort of SS patients, isolated anti-Ro52 represents a severe subset of SS, and is associated with the presence of cryoglobulinaemia. We therefore provide clinical relevance to the stratification of SS patients by their sero-reactivities. It is possible that the autoantibody patterns may be immunological epiphenomena of the underlying disease process, and further work is required to unearth the mechanisms of the differential clinical phenotypes.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115548/fullanti-Ro52/TRIM21autoantibodiescryoglobulinaemiarheumatoid factor, Ro/LaSjögren’s syndrome
spellingShingle Adrian Y. S. Lee
Adrian Y. S. Lee
Trishni Putty
Trishni Putty
Ming-Wei Lin
Ming-Wei Lin
Sanjay Swaminathan
Sanjay Swaminathan
Dan Suan
Dan Suan
Tim Chataway
Rogier M. Thurlings
Tom P. Gordon
Tom P. Gordon
Jing Jing Wang
Jing Jing Wang
Joanne H. Reed
Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
Frontiers in Immunology
anti-Ro52/TRIM21
autoantibodies
cryoglobulinaemia
rheumatoid factor, Ro/La
Sjögren’s syndrome
title Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
title_full Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
title_fullStr Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
title_full_unstemmed Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
title_short Isolated anti-Ro52 identifies a severe subset of Sjögren’s syndrome patients
title_sort isolated anti ro52 identifies a severe subset of sjogren s syndrome patients
topic anti-Ro52/TRIM21
autoantibodies
cryoglobulinaemia
rheumatoid factor, Ro/La
Sjögren’s syndrome
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115548/full
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