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.
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OBJECTIVES: Autoantibodies directed against Ro52/TRIM21 are common in systemic sclerosis (SSc) but their clinical significance remains uncertain. The aim of this study was to assess the clinical correlates and survival of subjects with monospecific anti-Ro52/TRIM21 antibodies, i.e. anti-Ro52/TRIM21 antibodies in the absence of other SSc-related antibodies. METHODS: A tri-nation (Canada, Australia, USA) cohort of 1574 SSc subjects was formed, demographic and clinical variables were harmonised and sera were tested using a common diagnostic platform. Statistical analyses were performed to determine associations between the presence of monospecific anti-Ro52/TRIM21 antibodies and outcomes of interest, including interstitial lung disease (ILD) and survival. RESULTS: 103 (6.5%) had monospecific anti-Ro52/TRIM21 antibodies, 324 (20.6%) had anti-Ro52/TRIM21 antibodies overlapping with other SSc-related antibodies and 1147 (72.9%) were negative for anti-Ro52/TRIM21 antibodies. Monospecific subjects were less likely to be White compared to negative subjects (68% vs. 82%, odds ratio (OR) 0.48, 95% confidence interval (CI) 0.30-0.75, p=0.0011). ILD was the only clinical variable significantly associated with monospecific anti-Ro52/TRIM21 antibodies compared to negative subjects (adjusted OR 2.70, 95% CI 1.75-4.14, p<0.0001). Subjects with monospecific anti-Ro52/TRIM21 antibodies were at significantly increased risk of death compared to subjects without anti-Ro52/TRIM21 antibodies (log rank p=0.0003; adjusted hazard ratio (HR) 1.87, 95% CI 1.24-2.82, p=0.0029). CONCLUSIONS: The results obtained from this unique tri-nation cohort represent the strongest evidence to date that anti-Ro52/TRIM21 antibodies are independently associated with the presence of ILD and poor survival in SSc. These data provide strong support for the predictive and prognostic value of this serological biomarker in SSc.
