Abstract
Although antibodies targeting Ro52 protein/TRIM21 are commonly detected in systemic autoimmune rheumatic disorders (SARDs), their clinical significance and pathobiologic role remains incompletely understood. Objectives. We aimed to define clinical relevance and immunological associations of anti-Ro52/TRIM21 positivity in a cohort of patients with SARDs. Methods. We retrospectively reviewed medical records of 97 consecutive SARDs who attended at least once our Rheumatology Department between March 2016 and June 2017. Clinical manifestations, rheumatoid factor (RF) (Latex and Waalter-Rose tests), antinuclear antibodies (ANA>1:100, immunofluorescence assays) as well as detailed ANA profile (nRNP/Sm, Sm, SS-A/Ro, Ro52/TRIM21, SS-B/La, Scl-70, PM/Scl, Jo-1, CENP-B, PCNA, dsDNA, nucleosome, histone, P-ribosomal protein, AMA-M2, DFS70) (line immunoblot assay) were systematically evaluated. Statistical analysis was performed in SPSS19.0, assuming significance for p<0.05; the chi-squared test was applied to determine the association between anti-Ro52/TRIM21 status and clinical manifestations of SARDs. Results. Only 27 patients (23.7%) had anti-Ro52/TRIM21 positive disease and were further analyzed. Isolated anti-Ro52/TRIM21 were detected in 7/27 (25.9 %) cases, while the majority had dual anti-Ro52/TRIM21 positivity and anti-Ro (n=7/20; 35%), anti-dsDNA (n=3/20, 15%), anti-Jo1 (n=3/20, 15%), anti-centromere B (n=2/20; 10%), anti-Scl70 (n=2/20; 10%), anti-RNP/Sm (n=2/20, 10%), anti-Pm/Scl (n=1/20, 5%), and RF (n=13; 65%). Patients were classified as Sjögren’s syndrome (n=7/27, 25.9%), myositis (n=3/27, 11.1%), systemic lupus erythematosus (n=3/27, 11.1%), systemic sclerosis (n=4/27,15.2%), mixed (n=3/27, 11.1%) or undifferentiated connective tissue disease (n=7/27, 25.9%). More than half of anti-Ro52/TRIM21 positive patients presented with interstitial lung fibrosis (18/27, 66.6%), insolated (33.3%) or in association with anti-Jo1 (33.3%). Conclusions. Anti-Ro52/TRIM21 antibodies should be systematically evaluated in patients with SARDs, as anti-Ro52 positivity (either isolated or in combination with different other ANA specificities) may be associated with definite clinical features. Anti-Ro52/TRIM21 may be useful in identifying a subgroup of patients at risk for developing certain symptoms (particularly interstitial lung disease) of SARDs, with specific therapeutic outcomes.
Highlights
Anti-Ro52/TRIM21 antibodies should be systematically evaluated in patients with systemic autoimmune rheumatic disorders (SARDs), as antiRo52 positivity may be associated with definite clinical features
Anti-Ro52/TRIM21 may be useful in identifying a subgroup of patients at risk for developing certain symptoms of SARDs, with specific therapeutic outcomes
Recognized as tripartite motif-containing 21 or TRIM21, Ro52 is a 52 kDa protein that acts as a shared target for autoantibodies in various systemic rheumatic and non-rheumatic autoimmune pathology including Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic myositis – polymyositis/ dermatomyositis (PM/DM), mixed or undifferentiated connective tissue diseases (MCTD/ UCTD), rheumatoid arthritis, neonatal lupus erythematosus, primary biliary cirrhosis and autoimmune hepatitis [1,2]
Summary
Ro52 is usually involved in the complex processes of cell signalling and immunity, regulating cellular oxidative stress and mediating apoptosis [5,6]. Why and how this protein becomes antigenic and ROMANIAN JOURNAL OF RHEUMATOLOGY – VOLUME XXVI, NO. Antibodies against Ro52 are frequently tested in clinical practice and are part of the standard extractable nuclear antigen (ENA) panel [2]. The clinical relevance of antibodies to Ro52/TRIM21 in a broad spectrum of systemic autoimmune conditions was recently updated, their pathobiologic, diagnostic and prognostic roles remain incompletely understood [1]
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