Clinical characteristics of anti-Ro52/TRIM21-positive versus anti-Ro52/TRIM21-negative patients with anti-synthetase syndrome: a retrospective cohort study

OBJECTIVES: Anti-Ro52/TRIM21 antibodies have been linked to interstitial lung disease (ILD) severity in anti-synthetase syndrome (ASS), but their broader clinical relevance remains uncertain. We compared clinical, pulmonary, treatment, and outcome characteristics according to Anti-Ro52/TRIM21 status in a Swiss single-center cohort. METHODS: This retrospective cohort included patients diagnosed with ASS followed at Geneva University Hospitals from 2010 to 2024 who met the Connors criteria and had available anti-Ro52 kDa antibody testing. Group comparisons used two-sided Wilcoxon rank-sum or Fisher's exact tests, and exploratory associations were assessed using univariate Firth logistic regression. RESULTS: Among 295 screened records, 38 patients were included (16 anti-Ro52/TRIM21-positive patients and 22 anti-Ro52/TRIM21-negative); mean follow-up was 6.63 ± 5.34 years. Pulmonary involvement was numerically more frequent in anti-Ro52/TRIM21-positive patients (15/16 [93.8%] vs 17/22 [77.3%]; p = 0.37), but the regression association was not statistically significant (OR 3.27, 95% CI 0.66-24.51; p = 0.18). Severe infections occurred in 6/16 (37.5%) versus 1/22 (4.5%) patients (p = 0.028); the univariate OR was 12.60 (95% CI 1.82-255.43; p = 0.027). Baseline DLCO and FVC were similar between the groups (p = 0.598 and p = 0.824, respectively). Treatment patterns differed descriptively, including greater use of biologic in some treatment lines among anti-Ro52/TRIM21-positive patients. CONCLUSIONS: In this small exploratory cohort, severe infections were more frequent among anti-Ro52/TRIM21-positive patients in unadjusted analyses, whereas pulmonary involvement differed only numerically and baseline pulmonary function was similar. Treatment-related confounding factors and the imprecise infection estimate limit interpretation. Larger multicenter studies with standardized longitudinal pulmonary assessment and appropriately adjusted analyses accounting for treatment exposure are needed. Key Points • Pulmonary involvement was numerically more frequent in anti-Ro52/TRIM21-positive patients, but the difference was not statistically significant. • Severe infections were more frequent in anti-Ro52/TRIM21-positive patients in unadjusted analyses, but the estimate was imprecise and potentially confounded by treatment exposure. • Baseline muscle involvement, DLCO, FVC, and prednisone doses at measured time points were broadly similar between the groups. • Differences in steroid-sparing treatment patterns were descriptive but should not be interpreted as evidence of a distinct or more severe disease course.