Primary biliary cirrhosis (PBC) is a chronic, destructive autoimmune liver disease characterized by the presence of antimitochondrial autoantibodies in patient’s serum and T cell-mediated destruction of the biliary epithelial cells lining the small intrahepatic bile ducts. Patient sera are characterized by a high frequency (greater than 95%) of autoantibodies directed to a mitochondrial antigen, identified as the E2 component of the pyruvate dehydrogenase multienzyme complex (PDC-E2). PDC-E2 contains both an amino-terminal lipoyl-bearing domain and a carboxy-terminal catalytic domain. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-bearing site. Two conformationally alternative forms of the PDC-E2 protein have been revealed by immunoblotting. The immunodominant autoepitopes of the autoantigens correspond to the inner lipoyl domain. A significant number of asymptomatic patients found to have antibodies to PDC-E2 are at high risk of developing primary biliary cirrhosis.
