Dual positivity for Anti-Ro52 and Anti-Ro60 antibodies is linked to greater organ involvement and disease progression in systemic sclerosis.

Objectives: To investigate the distinct and combined effects of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies on the clinical features and prognosis of patients with systemic sclerosis (SSc).

Methods: A single-center observational study was conducted using data from the Renji Scleroderma Longitudinal Cohort (Renji-SLOC), including 379 SSc patients with at least 1 year of follow-up. The patients were categorized into four groups based on serological status: double-negative (Ro52/Ro60), isolated anti-Ro52/TRIM21 positive (Ro52), isolated anti-Ro60/SSA positive (Ro60), double-positive (Ro52/Ro60). Clinical features and disease progression were analyzed using multivariable logistic regression and survival analysis.

Results: Among 379 patients, 12.7% (n=48) were double-positive. Notably, 43.6% of Ro52-positive patients were also Ro60-positive, and 62.3% of Ro60-positive patients were Ro52-positive, indicating significant co-occurrence. Double-positive patients exhibited significantly higher rates of ILD (79.2%), PAH (25.0%), digital ulcers (41.7%), and gastrointestinal symptoms (79.2%). Multivariable analysis confirmed that double positivity independently increased risks of ILD (adjusted OR=2.27, 95% CI=1.02-5.14), PAH (adjusted OR=2.24, 95% CI=1.03-4.84), digital ulcers (adjusted OR=3.12, 95% CI=1.57-6.20), and gastrointestinal involvement (adjusted OR=2.28, 95% CI=1.08-4.81). Survival analysis demonstrated significantly worse progression-free survival in double-positive patients (adjusted HR=1.90, 95% CI=1.24-2.90 for overall progression; adjusted HR=2.20, 95% CI=1.36-3.57 for ILD progression, both p<0.05).

Conclusion: Dual positivity for anti-Ro52 and anti-Ro60 antibodies identifies a distinct SSc subgroup with severe organ involvement and accelerated disease progression, particularly ILD. These findings highlight the prognostic value of combined antibody testing and underscore the need for vigilant monitoring in double-positive patients.