Clinical significance of anti-Ro52 (TRIM21) antibodies in adult patients with connective tissue diseases


      • Anti-Ro52 antibodies were strongly associated with the prevalence of interstitial lung disease at the diagnosis of connective tissue disease, even after adjusting for the coexistence of anti-Ro60 antibodies.
      • Anti-Ro52 antibodies positivity should lead clinicians to careful screening of interstitial lung disease at the diagnosis of connective tissue disease.
      • Anti-Ro52 antibodies could represent a useful severity marker of connective tissue diseases.



      Clinical significance of anti-Ro52 antibodies in connective tissue diseases (CTD) is controversial. Anti-Ro52 antibodies might be associated with a more severe CTD phenotype, especially interstitial lung disease (ILD). The aims of this study were to evaluate ILD prevalence and severity, the prevalence of micro- or macroangiopathy and CTD-associated cancers in CTD with anti-Ro52 antibodies.


      CTD patients with anti-Ro52 antibody screening by immunoblot at diagnosis were enrolled. Two groups were retrospectively formed according to the presence of anti-Ro52 antibodies with an unbiased 1:1 matching on CTD types. Unsupervised multiple correspondence analysis and hierarchical clustering analysis were used to aggregate anti-Ro52 positive patients in subgroups.


      408 CTD patients were included. Anti-Ro52 antibodies were detected in 33 % of CTD patients. Anti-Ro52 antibodies were associated with ILD at CTD diagnosis (47.8% vs. 23.0%, OR 3.3 95% IC 1.4 to 8.0, p = 0.008), even after adjusting for the presence of anti-Ro60 antibodies, especially in patients with antisynthetase syndrome, primary Sjögren syndrome and systemic sclerosis. Micro- or macroangiopathy was more frequent in anti-Ro52 positive CTD patients (18.6% vs. 9.7%, p = 0.02) and CTD patients with anti-Ro52 antibodies experienced more frequent relapses and required more immunosuppressive drugs. Clusters 4 and 5 identified anti-Ro52 positive CTD patients with severe ILD and with clinical features of systemic sclerosis or antisynthetase syndrome respectively.


      We found that anti-Ro52 antibodies were independently associated with ILD in CTD patients irrespective of CTD type. Anti-Ro52 antibodies could be associated with severity and a more relapsing disease course in CTD patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lee S.A.
        • Kahng J.
        • Kim Y.
        • Park Y.J.
        • Han K.
        • Kwok S.K.
        • et al.
        Comparative study of immunofluorescent antinuclear antibody test and line immunoassay detecting 15 specific autoantibodies in patients with systemic rheumatic disease.
        J Clin Lab Anal. 2012; 26: 307-314
        • Wolin S.L.
        • Steitz J.A.
        The Ro small cytoplasmic ribonucleoproteins: identification of the antigenic protein and its binding site on the Ro RNAs.
        Proc Natl Acad Sci USA. 1984; 81: 1996-2000
        • Ben-Chetrit E.
        • Chan E.K.
        • Sullivan K.F.
        • Tan E.M.
        A 52-kD protein is a novel component of the SS-A/Ro antigenic particle.
        J Exp Med. 1988; 167: 1560-1571
        • Koenig M.
        • Fritzler M.J.
        • Targoff I.N.
        • Troyanov Y.
        • Senécal J.L.
        Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes.
        Arthritis Res Ther. 2007; 9: R78
        • Hudson M.
        • Pope J.
        • Mahler M.
        • Tatibouet S.
        • Steele R.
        • Baron M.
        • et al.
        Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis.
        Arthritis Res Ther. 2012; 14: R50
        • Montano-Loza A.J.
        • Shums Z.
        • Norman G.L.
        • Czaja A.J.
        Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis.
        Liver Int. 2012; 32: 85-92
        • Hervier B.
        • Rimbert M.
        • Colonna F.
        • Hamidou M.A.
        • Audrain M.
        Clinical significance of anti-Ro/SSA-52 kDa antibodies: a retrospective monocentric study.
        Rheumatol Oxf Engl. 2009; 48: 964-967
        • Menéndez A.
        • Gómez J.
        • Escanlar E.
        • Caminal-Montero L.
        • Mozo L.
        Clinical associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies: diagnostic utility of their separate detection.
        Autoimmunity. 2013; 46: 32-39
        • Marie I.
        • Hatron P.Y.
        • Dominique S.
        • Cherin P.
        • Mouthon L.
        • Menard J.F.
        • et al.
        Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody.
        Semin Arthritis Rheum. 2012; 41: 890-899
        • Gunnarsson R.
        • El-Hage F.
        • Aaløkken T.M.
        • Reiseter S.
        • Lund M.B.
        • Garen T.
        • et al.
        Associations between anti-Ro52 antibodies and lung fibrosis in mixed connective tissue disease.
        Rheumatol Oxf Engl. 2016; 55: 103-108
        • Shi J.
        • Li S.
        • Yang H.
        • Zhang Y.
        • Peng Q.
        • Lu X.
        • et al.
        Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies.
        J Rheumatol. 2017; 44: 1051-1057
        • Wodkowski M.
        • Hudson M.
        • Proudman S.
        • Walker J.
        • Stevens W.
        • Nikpour M.
        • et al.
        Monospecific anti-Ro52/TRIM21 antibodies in a tri-nation cohort of 1574 systemic sclerosis subjects: evidence of an association with interstitial lung disease and worse survival.
        Clin Exp Rheumatol. 2015; 33: 131-135
        • Dong X.
        • Zhou J.
        • Guo X.
        • Li Y.
        • Xu Y.
        • Fu Q.
        • et al.
        A retrospective analysis of distinguishing features of chest HRCT and clinical manifestation in primary Sjögren's syndrome-related interstitial lung disease in a Chinese population.
        Clin Rheumatol. 2018; 37: 2981-2988
        • Sabbagh S.
        • Pinal-Fernandez I.
        • Kishi T.
        • Targoff I.N.
        • Miller F.W.
        • Rider L.G.
        • et al.
        Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis.
        Ann Rheum Dis. 2019; 78: 988-995
        • Aletaha D.
        • Neogi T.
        • Silman A.J.
        • Funovitis J.
        • Felson D.T.
        • Bingham C.O.
        • et al.
        rheumatoid arthritis classification criteria: an American college of rheumatology/European league against rheumatism collaborative initiative.
        Ann Rheum Dis. 2010; 69: 580-588
        • Petri M.
        • Orbai A.M.
        • Alarcón G.S.
        • Gordon C.
        • Merrill J.T.
        • Fortin P.R.
        • et al.
        Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus.
        Arthritis Rheum. 2012; 64: 2677-2686
        • Shiboski C.H.
        • Shiboski S.C.
        • Seror R.
        • Criswell L.A.
        • Labetoulle M.
        • Lietman T.M.
        • et al.
        American college of rheumatology/European league against rheumatism classification criteria for primary sjögren's syndrome: a consensus and data-driven methodology involving three international patient cohorts.
        Ann Rheum Dis. 2016; 76: 9-16
        • van den Hoogen F.
        • Khanna D.
        • Fransen J.
        • Johnson S.R.
        • Baron M.
        • Tyndall A.
        • et al.
        classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative.
        Ann Rheum Dis. 2013; 72: 1747-1755
        • Bohan A.
        • Peter J.B.
        Polymyositis and dermatomyositis (second of two parts.
        N Engl J Med. 1975; 292: 403-407
        • Sharp G.C.
        Diagnostic criteria for classification of MCTD.
        in: Kasukawa R. Sharp G.C. Mixed connective tissue diseases and antinuclear antibodies. Elsevier, Amsterdam1987: 23-32
        • Alarcón-Segovia D.
        • Villareal M.
        Classification and diagnostic criteria for mixed connective tissue disease.
        in: Kasukawa R. Sharp G.C. Mixed connective tissue diseases and antinuclear antibodies. Elsevier, Amsterdam1987: 33-40
        • Kasukawa R.
        • Tojo T.
        • Miyawaki S.
        Preliminary diagnostic criteria for classification of mixed connective tissue disease.
        in: Kasukawa R. Sharp G.C. Mixed connective tissue diseases and antinuclear antibodies. Elsevier, Amsterdam1987: 41-47
        • Mosca M.
        • Neri R.
        • Bombardieri S.
        Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria.
        Clin Exp Rheumatol. 1999; 17: 615-620
        • Nathan S.D.
        • Shlobin O.A.
        • Weir N.
        • Ahmad S.
        • Kaldjob J.M.
        • Battle E.
        • et al.
        Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium.
        Chest. 2011; 140: 221-229
        • Zappala C.J.
        • Latsi P.I.
        • Nicholson A.G.
        • Colby T.V.
        • Cramer D.
        • Renzoni E.A.
        • et al.
        Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis.
        Eur Respir J. 2010; 35: 830-836
        • Simonneau G.
        • Montani D.
        • Celermajer D.S.
        • Denton C.P.
        • Gatzoulis M.A.
        • Krowka M.
        • et al.
        Haemodynamic definitions and updated clinical classification of pulmonary hypertension.
        Eur Respir J. 2019; : 53
        • Wu S.
        • Tang X.
        • Wu L.
        • Lu L.J.
        • Feng X.
        Association of anti-Ro52 autoantibodies with interstitial lung disease in connective tissue diseases.
        Ann Rheum Dis. 2019;
        • Park J.H.
        • Kim D.S.
        • Park I.N.
        • Jang S.J.
        • Kitaichi M.
        • Nicholson A.G.
        • et al.
        Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes.
        Am J Respir Crit Care Med. 1 avr. 2007; 175 (705–11)
        • Bauhammer J.
        • Blank N.
        • Max R.
        • Lorenz H.M.
        • Wagner U.
        • Krause D.
        • et al.
        Rituximab in the treatment of Jo1 antibody-associated antisynthetase syndrome: Anti-Ro52 positivity as a marker for severity and treatment response.
        J Rheumatol. 2016; 43: 1566-1574
        • Burbelo P.D.
        • Ching K.H.
        • Han B.L.
        • Bush E.R.
        • Reeves W.H.
        • Iadarola M.J.
        Extraordinary antigenicity of the human Ro52 autoantigen.
        Am J Transl Res. 2010; 2: 145-155
        • Sternbaek L.
        • Friis T.
        • Houen G.
        Determination of autoantibodies by line immunoblotting.
        Methods Mol Biol. 2019; 1901: 255-262
        • Lee A.Y.S.
        A review of the role and clinical utility of anti-Ro52/TRIM21 in systemic autoimmunity.
        Rheumatol Int. 2017; 37: 1323-1333