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Abstract

Sera from patients with primary biliary cirrhosis contain autoantibodies that recognize mitochondrial proteins. Five of the target autoantigens have now been identified as enzymes of three related multienzyme complexes: the pyruvate dehydrogenase complex, the branched chain α-ketoacid dehydrogenase complex and the α-ketoglutarate dehydrogenase complex. Each complex consists of component enzymes designated E1, E2 and E3. In this report, we confirm that primary biliary cirrhosis sera react with dihydrolipoamide succinyltransferase, the E2 component of α-ketoglutarate dehydrogenase complex. Seventy-three of 188 (39%) primary biliary cirrhosis sera reacted with α-ketoglutarate dehydrogenase complex-E2 when immunoblotted against purified α-ketoglutarate dehydrogenase complex; one of these sera also reacted with the E1 component. In addition, primary biliary cirrhosis sera possessing α-ketoglutarate dehydrogenase complex-E2 reactivity specifically inhibited enzyme function of α-ketoglutarate dehydrogenase complex. Enzyme activity was not affected by primary biliary cirrhosis sera that contained autoantibodies to pyruvate dehydrogenase complex-E2 and/or branched chain α-ketoacid dehydrogenase complex-E2, which lacked α-ketoglutarate dehydrogenase complex-E2 reactivity. Furthermore, affinity-purified primary biliary cirrhosis sera against α-ketoglutarate dehydrogenase complex-E2 inhibited only α-ketoglutarate dehydrogenase complex activity but did not alter enzyme activity of either pyruvate dehydrogenase complex or branched chain α-ketoacid dehydrogenase complex. Finally, α-ketoglutarate dehydrogenase complex-E2 specific affinity-purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain α-ketoacid dehydrogenase complex. These data demonstrate that the E2 component of α-ketoglutarate dehydrogenase complex is recognized by a distinct population of autoantibodies separate from autoantibodies that recognize pyruvate dehydrogenase complex-E2 or branched chain α-ketoacid dehydrogenase complex-E2. Our data further suggest that these autoantibodies are directed toward a functional domain of this enzyme.(HEPATOLOGY 1990;11:975-981.).