Pathogenic role of anti-nuclear autoantibodies in systemic sclerosis: insights from other rheumatic diseases

Abstract

Systemic sclerosis (SSc) is a severe autoimmune disease characterized by vasculopa-thy, fibrosis, and dysregulated immunity, with hallmark autoantibodies targeting nu-clear antigens such as centromere protein (ACA) and topoisomerase I (ATA). Theseautoantibodies are highly prevalent and disease-specific, rarely coexisting, thus serv-ing as crucial biomarkers for SSc diagnosis. Despite their diagnostic value, their rolesin SSc pathogenesis remain unclear. This review summarizes current literature on ACAand ATA in SSc, comparing them to autoantibodies in other rheumatic diseases toelucidate their potential pathogenic roles. Similarities are drawn with anti-citrullinatedprotein antibodies (ACPA) in rheumatoid arthritis, particularly regarding disease spec-ificity and minimal pathogenic impact of antigen binding. In addition, differences be-tween ANA and ACPA in therapeutic responses and Fab glycosylation patterns arereviewed. While ACA and ATA are valuable for disease stratification and monitoringactivity, understanding their origins and the associated B cell responses is critical foradvancing therapeutic strategies for SSc.