Clinical and Serological Heterogeneity in Anti‑centromere Antibody‑positive Individuals: A Tertiary Center Analysis

Clinical and Serological Heterogeneity in Anti‑centromere Antibody‑positive Individuals: A Tertiary Center Analysis

Objectives: Anticentromere antibodies (ACAs) are classically associated with limited cutaneous systemic sclerosis (SSc) but are increasingly detected in a variety of autoimmune and non‑autoimmune conditions. This study aimed to characterize the diagnostic distribution, clinical manifestations, and autoantibody profiles of ACA‑positive patients in a tertiary medical center. Methods: We retrospectively analyzed 179 consecutive ACA‑positive individuals with confirmed AC‑3 pattern on human epithelial type‑2 indirect immunofluorescence (March 2023–April 2024). Demographic characteristics, clinical features, and autoantibody profiles were compared among SSc spectrum and non‑SSc groups, rheumatoid arthritis (RA) and Sjögren’s disease (SjD) subsets, and anti‑SSA/SSB‑positive and anti‑SSA/SSB‑negative patients. Results: SSc spectrum accounted for 22.3% of ACA‑positive patients, whereas 19.0% had other connective tissue diseases, 6.1% had organ‑specific autoimmune diseases, and 50.8% had nonautoimmune conditions. Raynaud’s phenomenon (77.5% vs. 28.1%, P < 0.001) and skin induration (65.0% vs. 4.3%, P < 0.001) distinguished SSc spectrum from non‑SSc patients, whereas pruritic rashes were observed only in nonsystemic‑sclerosis diagnoses. ACA‑positive RA patients were younger with more arthralgia and anticyclic citrullinated peptide (anti‑CCP) positivity but fewer sicca symptoms than ACA‑positive SjD patients. Among ACA‑positive patients, those double‑positive for ACA and anti‑SSA/SSB accounted for 18.7% (26/139) of the non‑SSc group and demonstrated markedly higher SjD prevalence (38.5% vs. 5.3%, P < 0.001), sicca symptoms, elevated antinuclear antibodies titers, and anti‑Ro52 positivity compared with anti‑SSA/SSB‑negative patients. Conclusions: ACA positivity defines a heterogeneous polyautoimmune spectrum; SSc represented only one‑fifth of cases. The clinical phenotype is associated with coexisting disease‑defining autoantibodies–anti‑CCP in RA and anti‑SSA/SSB in SjD–rather than ACA alone, necessitating phenotype‑oriented interpretation and comprehensive clinical assessment rather than presumptive SSc diagnosis.