Utility of an extended 12-autoantibody panel in systemic sclerosis: clinical and prognostic implications in a real-life cohort.

BACKGROUND AND OBJECTIVE: Systemic sclerosis (SSc) is a highly heterogeneous autoimmune disease in which early prognostic stratification is essential. We analysed the clinical and evolutionary associations of 12 SSc-related autoantibodies (Scl-70, CENP-A, CENP-B, RNApol-III, U3-RNP, Th/To, NOR90, U1-RNP, PM/Scl100, PM/Scl75, Ku, and Ro52) in patients with suspected or diagnosed SSc. PATIENTS AND METHODS: A study was conducted on 186 patients (110 of whom met SSc classification criteria) who tested positive for at least one of 12 antigens detected simultaneously via immunoblotting between 2019 and 2022. We analysed the phenotypic associations of each autoantibody and the time to development of interstitial lung disease (ILD) or elevated pulmonary artery systolic pressure (PASP). RESULTS: Most patients were female (81.7%), with a mean age at onset of 50.4 ± 15.1 years. Anti-Scl-70 was associated with diffuse SSc and was the main predictor of risk for ILD (HR: 2.43; 95% CI: 1.58-3.75) and elevated PASP (HR: 2.61; 95% CI: 1.09-3.68). Anti-CENP antibodies were linked to limited SSc and a lower incidence of ILD and elevated PASP (HR: 0.20; p <  0.001 and HR: 0.33; p =  0.013, respectively). Anti-RNApol-III showed high early pulmonary morbidity (52.9% for ILD and 47.1% for elevated PASP), with one-third of the events occurring within the first three years of evolution. Isolated anti-Ro52 positivity was associated with lower clinical expressivity and fewer evolutionary complications. CONCLUSIONS: Autoantibody profiling via immunoblotting identifies distinct clinical and evolutionary phenotypes in patients with suspected or diagnosed SSc. Anti-RNApol-III is associated with early pulmonary involvement, while anti-Ro52 monospecificity is linked to a more favourable clinical course.