Isolated Anti‐ <scp>SS</scp> ‐A Antibody Seropositivity as a Poor Prognostic Factor in Systemic Sclerosis: Insights From a Cohort of 307 Cases

Systemic sclerosis is an autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Anti-SS-A antibodies (anti-SSA) have been reported to confer severe clinical manifestations in some Western and Japanese cohorts. We aimed to determine whether anti-SSA seropositivity affects clinical outcomes in Japanese patients. We retrospectively analyzed 307 Japanese patients with systemic sclerosis who underwent initial evaluation between January 2011 and March 2020 in our clinic. "Isolated" anti-SSA seropositivity was defined as positivity for anti-SSA in the absence of anti-topoisomerase I, anti-centromere, anti-RNA polymerase III, and anti-U1 ribonucleoprotein antibodies. Overall survival was defined as time to all-cause mortality, and progression-free survival was defined as time to disease progression necessitating intensified therapy. Cox proportional hazards models were employed to estimate hazard ratios and 95% confidence intervals. For patients with "isolated" anti-SSA seropositivity, further investigation for SSc-related autoantibodies was conducted utilizing Autoantibody Array Assay (A-Cube). Anti-SSA were detected in 31.3% of patients. Although anti-SSA seropositivity overall correlated with interstitial lung disease, it was not independently associated with overall survival or progression-free survival. In contrast, "isolated" anti-SSA seropositivity emerged as an independent risk factor for both shorter overall survival (hazard ratio 21.7, 95% confidence interval 5.57-84.8) and progression-free survival (hazard ratio 4.18, 95% confidence interval 1.05-16.7). Expanded serologic testing revealed additional autoantibodies implicated in severe SSc phenotypes. These findings underscore the importance of routinely assessing anti-SSA and highlight the need for autoantibody screening in depth in this subpopulation.