The pyruvate dehydrogenase complex as a target autoantigen in primary biliary cirrhosis

Mitochondrial autoantigens and their B and T cell autoepitopes have been we ll defined in primary biliary cirrhosis (PBC). However, the relationships o f the antimitochondrial antibodies and the mechanisms of bile duct destruct ion in PBC remain an enigma. The serological hallmark of PBC remains the pr esence of antibodies to mitochondria, particularly to the E2 component of t he pyruvate dehydrogenase complex (PDC-E2). However, several mechanisms may now be proposed which may explain the immune-mediated bile duct damage in PBC. These include the possible role of T cell-mediated cytotoxicity as wel l as the interaction between the IgA class of antimitochondrial antibodies and the mitochondrial autoantigens. A prominent feature in this discussion is the highly directed and specific immune response to the mitochondrial an tigens, including PDC-E2 as well as other members of the 2-oxo-acid dehydro genase complexes. Ultimately, the mechanisms that lead to this immune react ion should provide data on other questions in PBC, including the reasons fo r female predominance, the absence of PBC in children and the relative inef fectiveness of immunosuppressive agents.