Anti-centromere antibody positivity: a spectrum of clinical diagnoses and immunological patterns in a large patient cohort.

Anti-centromere antibody (ACA) positivity is recognized in diverse autoimmune diseases beyond systemic sclerosis (SSc). This study aimed to comprehensively characterize the clinical spectrum and serological profiles of ACA-positive (anti-CENP-B-positive) patients in a large cohort. This retrospective study analyzed 1736 ACA-positive patients presenting from January 2016 to December 2023. Patients were categorized into defined systemic rheumatic and autoimmune liver disease group (Defined disease group); undifferentiated connective tissue disease (UCTD); symptomatic seropositive patients without a classifiable disease (Unclassified group); and other defined systemic diseases. Clinical characteristics, antinuclear antibody (ANA) patterns, and concomitant autoantibodies were extracted and compared between the four groups and different disease groups. The cohort was predominantly female (94.38%), with a median age of 55 years. Defined disease group constituted 54.72% (n = 950), with primary biliary cholangitis (PBC, 23.80%) and Sjögren's syndrome (SS, 22.53%) being the most prevalent, followed by systemic lupus erythematosus (SLE, 13.92%), while SSc was only 6.16%. Patients in the defined disease group exhibited the highest proportion of strong anti-CENP-B reactivity (81.68%) and multiple autoantibodies (70.74%). Common co-occurring autoantibodies included anti-Ro52, anti-mitochondrial antibody M2 subtype (AMA-M2), anti-Sjögren syndrome A (anti-SSA), and anti-nuclear Ribonucleoprotein/Smith (anti-nRNP/Sm). Strong anti-CENP-B reactivity predominated in PBC (90.18%), SS (87.74%), autoimmune hepatitis (AIH, 91.53%), SSc (89.66%), and overlap syndrome (87.34%), whereas weak or moderate reactivity was relatively more frequent in SLE and rheumatoid arthritis (RA). Distinct ANA patterns and coexisting autoantibody profiles were observed across disease subgroups. Exploratory analyses further suggested that strong anti-CENP-B reactivity was associated with enrichment of centromere ANA patterns (64.05%), AMA-M2 positivity (31.44%), and liver cirrhosis (11.76%). Anti-CENP-B-positive individuals represent a clinically heterogenous population with PBC and SS as the predominant defined autoimmune diseases. Distinct ANA patterns, coexisting autoantibody profiles, and anti-CENP-B reactivity may provide complementary information for clinical phenotyping and diagnostic evaluation. Key Points •Primary biliary cholangitis and Sjögren's syndrome, not systemic sclerosis, are the most common definitive autoimmune diseases in the large anti-CENP-B-positive patient cohort. •Distinct ANA patterns, coexisting autoantibody profiles, and anti-CENP-B reactivity were observed across different autoimmune phenotypes, supporting their complementary role in clinical phenotyping and diagnostic evaluation.