Antimitochondrial antibodies in primary biliary cirrhosis

In the last decade, the cloning and biochemical identification of mitochondrial autoantigens in primary biliary cirrhosis (PBC) as members of the 2-oxoacid dehydrogenase complex has greatly advanced the detection of antimitochondrial antibodies (AMA) and the understanding of the immunobiology of the disease. Here, we discuss the methods of detecting AMA and its isotypes, methods of epitope mapping, and using these methods in PBC liver immunohistochemistry and Ig gene usage. Increasing evidence, including the specific association of AMA with PBC, the unique similar but noncross-reactive conformational epitope of the lipoyl domains of the mitochondrial autoantigens, the specific binding of anti-PDC-E2 monoclonal antibodies and human combinatorial antibodies derived from PBC patients to the apical area of bile duct epithelial cells in PBC livers, and Ig gene usage of AMA, suggests that AMA is not an epiphenomenon of the disease but plays a significant role in the pathogenesis of PBC.