Inhibition of α-ketoglutarate dehydrogenase activity by a distinct population of autoantibodies recognizing dihydrolipoamide succinyltransferase in primary biliary cirrhosis
✍ Scribed by David R. Fregeau; Thomas Prindiville; Ross L. Coppel; Marshall Kaplan; E. Rolland Dickson; M. Eric Gershwin
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 774 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 a-ketoacid dehydrogenase complex and the a-ketoglutarate dehydrogenase complex. Each complex consists of component enzymes designated El, E2 and E3. In this report, we confirm that primary biliary cirrhosis sera react with dihydrolipoamide succinyltransferase, the E2 component of a-ketoglutarate dehydrogenase complex. Seventy-three of 188 (39%) primary biliary cirrhosis sera reacted with a-ketoglutarate dehydrogenase complex-E2 when immunoblotted against purified a-ketoglutarate dehydrogenase complex; one of these sera also reacted with the E l component. In addition, primary biliary cirrhosis sera possessing a-ketoglutarate dehydrogenase complex-E2 reactivity specifically inhibited enzyme function of a-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 a-ketoacid dehydrogenase complex-E2, which lacked a-ketoglutarate dehydrogenase complex-E2 reactivity. Furthermore, affinity-purified primary biliary cirrhosis sera against a-ketoglutarate dehydrogenase complex-E2 inhibited only a-ketoglutarate