Introduction
Anti-centromere antibodies (ACA) recognize centromere proteins, particularly CENP-B, the major reactive antigen. While primarily associated with Raynaud’s phenomenon, systemic sclerosis (SS), and other autoimmune-like conditions, ACA positivity can also be observed in primary biliary cholangitis (PBC), often overlapping with rheumatological diseases.
Aims & Methods
This study aimed to explore the association between CENP-B positivity and liver test abnormalities in patients without known liver disease, evaluate its overlap with rheumatological conditions, and assess whether co-positivity with other antibodies may predict liver dysfunction. We conducted a retrospective cohort study including consecutive patients with CENP-B positivity (via immunoblot) from January 2020 to December 2024. Data on liver function tests (LFTs), antinuclear antibody (ANA) patterns, immunoglobulin M (IgM), anti-gp210, anti-sp100, antimitochondrial antibodies (AMA), and liver biopsy results were analysed.
Results
A total of 48 CENP-B-positive patients without known liver disease were included (85.4% female; mean age 68.7 ± 21.5 years). Liver test abnormalities were present in 56.3% of patients, predominantly elevated gamma-glutamyl transferase (GGT) (35.4%), alanine transaminase (ALT) (10.4%), and aspartate transaminase (AST) (18.8%). IgM elevation was infrequent (6.3%), and antibody co-positivity varied (anti-gp210: 0%; anti-sp100: 4.2%; AMA: 8.3%; anti-pyruvate dehydrogenase autoantibodies [anti-PDH]: 10.4%). There was reference to Raynaud’s phenomenon in 25%, and 91.7% of patients had a rheumatological or autoimmune-like condition (SS: 25%, systemic lupus erythematosus: 6.3%). Patients with concurrent AMA and CENP-B positivity had significantly higher ALT (U=31.5, Z=2.112, p=0.031) and GGT (U=34.5, Z=1.997, p=0.043) levels, though this association was not observed with other LFTs (AST, alkaline phosphatase, and bilirubin), ANA patterns, or antibodies. None of the four patients with liver test abnormalities and concurrent CENP-B and AMA positivity underwent liver biopsy.
Conclusion
The findings suggest that CENP-B-positive patients, particularly those with concurrent AMA positivity, may be at increased risk of developing liver diseases within the PBC spectrum. This group may warrant closer clinical and laboratory surveillance to enable timely identification and management of potential hepatic involvement.
References
1. Vázquez-Abad D, Grodzicky T, Senécal JL. Anticentromere autoantibodies in patients without Raynaud's disease or systemic sclerosis. Clin Immunol. 1999;90(2):182-189 doi:10.1006/1998.4643
2. Onozuka Y, Shibata M, Yonezawa H. Clinical significance of anti-centromere antibody and anti-CENP-B antibody in sera of patients with primary biliary cirrhosis. Rinsho Byori. 1996;44(9):877-882.
3. Favoino E, Grapsi E, Barbuti G, Liakouli V, Ruscitti P, Foti C, Giacomelli R, Perosa F. Systemic sclerosis and primary biliary cholangitis share an antibody population with identical specificity. Clin Exp Immunol. 2023 Apr 7;212(1):32-38. doi: 10.1093/cei/uxad012
Disclosure
1. Vázquez-Abad D, Grodzicky T, Senécal JL. Anticentromere autoantibodies in patients without Raynaud's disease or systemic sclerosis. Clin Immunol. 1999;90(2):182-189 doi:10.1006/1998.4643
2. Onozuka Y, Shibata M, Yonezawa H. Clinical significance of anti-centromere antibody and anti-CENP-B antibody in sera of patients with primary biliary cirrhosis. Rinsho Byori. 1996;44(9):877-882.
3. Favoino E, Grapsi E, Barbuti G, Liakouli V, Ruscitti P, Foti C, Giacomelli R, Perosa F. Systemic sclerosis and primary biliary cholangitis share an antibody population with identical specificity. Clin Exp Immunol. 2023 Apr 7;212(1):32-38. doi: 10.1093/cei/uxad012
