Antibodies directed against the Ro/SS-A system, traditionally linked with autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome, are now gaining attention for their role in systemic sclerosis (SSc). This system comprises two distinct target proteins with unique biochemical and immunological functions and includes Ro60 (60 kDa) and Ro52 (52 kDa). Ro52, also known as TRIM21, belongs to the tripartite motif protein family and is involved in protein ubiquitination, regulation of pro-inflammatory responses such as interleukin-2 production, and apoptosis. In contrast, Ro60 is a component of small cytoplasmic ribonucleoprotein complexes (hY-RNA complexes) that bind misfolded non-coding RNAs for degradation and also contribute to cell survival following ultraviolet irradiation.
A recent single-center observational study from the Renji Scleroderma Longitudinal Cohort (Renji-SLOC) has provided important insights into the distinct and combined effects of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies in systemic sclerosis. The study included 379 patients with at least one year of follow-up, categorized into four serological groups: double-negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+).
Among the total cohort, 12.7% (n=48) were double-positive. A strong co-occurrence pattern was evident, with 43.6% of Ro52-positive patients also testing positive for Ro60, and 62.3% of Ro60-positive patients also testing positive for Ro52. Patients with dual positivity experienced markedly higher complication rates compared to other groups: interstitial lung disease (ILD) in 79.2%, pulmonary arterial hypertension (PAH) in 25.0%, digital ulcers in 41.7%, and gastrointestinal symptoms in 79.2%.
Multivariable logistic regression confirmed double positivity as an independent risk factor for these complications. The adjusted odds ratios (ORs) were 2.27 (95% CI=1.02–5.14) for ILD, 2.24 (95% CI=1.03–4.84) for PAH, 3.12 (95% CI=1.57–6.20) for digital ulcers, and 2.28 (95% CI=1.08–4.81) for gastrointestinal involvement.
Survival analysis further revealed significantly worse progression-free survival among double-positive patients. The adjusted hazard ratio (HR) for overall progression was 1.90 (95% CI=1.24–2.90), while the risk of ILD progression was more than doubled (HR=2.20, 95% CI=1.36–3.57). Both associations were statistically significant (p<0.05).
Published in Seminars in Arthritis and Rheumatism, this study is the first to characterize the individual and combined effects of anti-Ro52 and anti-Ro60 antibodies in a longitudinal SSc cohort, while also examining their prognostic implications. The findings highlight dual anti-Ro52/Ro60 seropositivity as an independent marker of multiorgan morbidity and accelerated disease progression, with particularly strong relevance to interstitial lung disease.
The authors concluded that combined antibody testing carries significant prognostic value and should be incorporated into clinical practice for systemic sclerosis. They emphasized the need for vigilant monitoring and prioritized surveillance in patients with dual positivity, identifying this subgroup as being at high risk for adverse outcomes.
References
- Yin H, Lin W, Jia C, Gu C, Zhao Z, Wu F, Li Q, Ma Y, Li X, Ding Z, Liu X, Liu X, Zhang L, Lu L. Dual positivity for Anti-Ro52 and Anti-Ro60 antibodies is linked to greater organ involvement and disease progression in systemic sclerosis. Semin Arthritis Rheum. 2025 Oct;74:152810.
- Robbins A, Hentzien M, Toquet S, Didier K, Servettaz A, Pham BN, Giusti D. Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases. Front Immunol. 2019 Mar 12;10:444.