Autoantibodies in Primary Biliary Cholangitis: From Classical Markers to Emerging Targets

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. PBC encompasses several clinical subtypes, including classical AMA-positive PBC (90-95% of cases), AMA-negative PBC (5-10%), and overlap syndromes such as AIH-PBC. These subtypes exhibit distinct serological profiles, with AMA-negative cases often presenting PBC-specific antinuclear antibodies (anti-gp210, anti-sp100) and overlap syndromes demonstrating combined autoantibody patterns characteristic of both conditions. Autoantibodies serve as central biomarkers for diagnosis, prognosis, and understanding disease pathogenesis. This review provides a comprehensive overview of classical and emerging autoantibodies associated with PBC, including AMA-M2, anti-gp210, anti-sp100, anti-KLHL12, and anti-RPL30. We discuss their diagnostic significance across PBC subtypes, pathogenic implications, and potential utility in patient stratification and therapeutic monitoring. Recent evidence suggests that bile acid-induced neoantigen formation, rather than classical loss of immune tolerance, may drive AMA production. Advances in autoantibody profiling, including subclass-specific analysis and multi-marker panels, may pave the way for personalized medicine and improved outcomes in PBC.

Keywords: anti-mitochondrial antibody (AMA); antinuclear antibody (ANA); autoantibodies; molecular mimicry; primary biliary cholangitis (PBC).

Figure 1

Characteristic ANA patterns in PBC.

Figure 2

Pathogenesis of PBC—failure of the biliary HCO₃⁻ “umbrella” leading to neoantigen formation and AMA production.