The serum levels of specific autoantibodies in systemic sclerosis predict a more severe skin involvement.

Background: Systemic sclerosis is a severe autoimmune disease characterized by fibrosis of the skin and internal organs. Systemic sclerosis is associated with the presence of three specific autoantibodies: anti-topoisomerase I, anti-centromere, and anti-RNA polymerase III autoantibodies, which have also been identified as prognostic factors. However, it remains unknown whether the prognosis also varies based on their serum levels.

Objectives: We aimed to assess the value of serum levels of systemic sclerosis-specific autoantibodies as biomarkers of disease severity and progression in systemic sclerosis.

Design: We conducted a post hoc longitudinal analysis of data of systemic sclerosis patients included in the Zurich EUSTAR cohort, who were positive for at least one of the three systemic sclerosis-specific autoantibodies.

Methods: The association between the levels of systemic sclerosis-specific autoantibodies and disease severity at baseline and during the follow-up was assessed by univariable and multivariable logistic and linear regressions.

Results: The serum levels of anti-topoisomerase I autoantibodies [β = 0.032 (95% confidence interval = 0.014 to 0.049), p < 0.001], anti-centromere [β = 0.002 (95% confidence interval = 0.001 to 0.003), p < 0.001], and anti-RNA polymerase III autoantibodies [β = 0.143 (95% confidence interval = 0.066 to 0.220), p < 0.001] were associated with the modified Rodnan Skin Score in univariable analysis at baseline. For anti-centromere [β = 0.002 (95% confidence interval = 0.001 to 0.003), p < 0.001] and anti-RNA polymerase III autoantibodies [β = 0.135 (95% confidence interval = 0.053 to 0.217), p = 0.002], this association also remained significant in multivariable analysis. In the longitudinal analysis, the levels of the three systemic sclerosis-specific autoantibodies did not predict changes in mRSS over 1 year.

Conclusion: Increased serum levels of all three autoantibodies predicted a more severe skin fibrosis. The results underscore the relevance of measuring the levels of systemic sclerosis-specific autoantibodies to enhance risk stratification in systemic sclerosis, with particular focus on skin involvement.