Autoantibodies in primary biliary cirrhosis: Recent progress in research on the pathogenetic and clinical significance

Abstract

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of the small- and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMA) in the serum. AMA are detected in over 90% of patients with PBC, whereas their prevalence in the general population is extremely low, varying from 0.16% to 1%. Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens. Moreover, recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex, which is not observed in the serum of normal individuals. These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens. While it is currently generally accepted that AMA are the most specific serological markers of PBC, more than 60 autoantibodies have been investigated in patients with PBC, and some have previously been considered specific to other autoimmune diseases. This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC. Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.

Keywords: Primary biliary cirrhosis; Autoantibodies; Anti-mitochondrial antibodies; Anticentromere antibodies; Anti-gp210 antibodies

Core tip: While the presence of antimitochondrial antibodies is pathognomonic to Primary biliary cirrhosis (PBC), more than 60 autoantibodies have been detected in patients with PBC. Antinuclear antibodies (ANA) become positive in approximately 30% to 50% of patients with PBC. Among ANA, anti-gp210 and anticentromere antibodies have been indicated as significant prognostic markers. Previous studies have shown that unique characteristics of biliary epithelial cells during apoptosis may result in the presence of a direct and specific immune response to mitochondrial autoantigens. Moreover, recent studies have indicated that chemicals originating from the environment are associated with a breakdown in the tolerance against mitochondrial autoantigens.