Document resource
Introduction Systemic sclerosis (SSc) is an autoimmune disease with interstitial lung disease (ILD) as a major cause of morbidity and mortality. Anti-Scl-70 antibodies are well-known markers of ILD, while anti-U11/U12RNP, although rare, have been associated with poor prognosis. We aimed to compare clinical features and outcomes of SSc patients with anti-U11/U12RNP versus anti-Scl-70 antibodies, focusing on event-free survival to ILD progression (FVC decline <50%, oxygen therapy, lung transplantation) or ILD-related deathMaterial and Methods A retrospective case-control study was conducted in SSc patients positive for anti-Scl-70 or anti-U11/U12RNP antibodies. Anti-U11/U12RNP antibodies were detected by in-house RNA immunoprecipitation assay and anti-Scl-70 antibodies by chemiluminescence immunoassay. Clinical characteristics and long-term outcomes were compared. Event-free survival from ILD diagnosis to progression or ILD-related death was analyzed using Kaplan-Meier curves and Cox regression.Results Among 117 patients (14 anti-U11/U12RNP, 103 anti-Scl-70) there were 84 (81.6%) women. Ever-smokers were more frequent in the anti-U11/U12RNP group (50% vs 16.5%, p=0.036) and diffuse cutaneous SSc was less common (14.3% vs 55.3%, p=0.05). Compared with anti-Scl-70, anti-U11/U12RNP patients showed lower prevalence of Raynaud’s phenomenon (78.6% vs 97.6%, p=0.016), higher prevalence of pulmonary hypertension (35.7% vs 14.6%, p=0.05). The frequency of ILD was high in both groups (100% vs 82.5%, p=0.1).In the ILD cohort (n=99), anti-U11/U12RNP patients showed higher rates of severe ILD outcomes: an absolute FVC <50% (64.3% vs 36.5%), oxygen chronic therapy (35.7% vs 10.6%, p=0.031) and lung transplantation (35.7% vs 12.9%, p=0.040). ILD-related mortality was similar (23% vs 20.8%). Kaplan-Meier curves (figure 1) illustrated a trend towards poorer event-free survival in the anti-U11/U12RNP group (a. Absolute decline of FVC<50%, b. Oxygen therapy requirement, c. Lung transplantation and d. ILD-related death).Although not statistically significant, hazard ratios consistently favored this tendency: absolute FVC decline <50% (HR 1.5, 95% CI 0.72–3.22, p=0.26), oxygen chronic therapy (HR 2.6, 95% CI 0.87–7.75, p=0.08) and lung transplantation (HR 2.02, 95% CI 0.7–5.85, p=0.19). Survival ratio was comparable between groups.Conclusions Patients with anti-U11/U12RNP generally experience ILD, and display distinct clinical features, including lower rates of dcSSc and Raynaud’s phenomenon, but higher rates of ever-smoking and pulmonary hypertension. Their prognosis tends to be the same or even worse compared with anti-Scl-70 patients, as evidenced by higher rates of end-stage lung disease-related events. Although not statistically significant, these trends align with previous reports and warrant confirmation in larger cohorts. Anti-U11/U12RNP may be a poor prognostic biomarker, supporting the risk stratification and tailored management of this high-risk subgroup.Abstract P.421 Figure 1