Abnormal expression of pyruvate dehydrogenase on bile ducts opens new fields in the pathogenesis of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by nonsuppurative destructive cholangitis (CNSDC) of interlobular bile ducts. The ducts with CNSDC are positive for HLA-A, B, C and -DR and also infiltrated and surrounded by immunocompetent cells, suggesting the participation of autoimmune mechanism. Target antigens of antimitochondrial antibodies (AMAs), characteristically and very frequently detected in PBC patients, are closely related to pyruvate dehydrogenase complex-E2 (PDC-E2) which has been recently shown to be expressed abnormally on the luminal side of interlobular bile ducts of PBC. AMAs can inhibit the enzyme activities of PDC-E2. T cells reactive with this enzyme have been recently cloned from the livers with PBC. Although unusual expression of PDC-E2 on the bile ducts, particularly on their luminal side, is observed, it is unclear whether this phenomenon is related primarily or secondarily to the cause of bile duct damages in PBC.