Fregeau D R, Prindiville T, Coppel R L, Kaplan M, Dickson E R, Gershwin M E
Division of Clinical Immunology, University of California, Davis 95616.
Hepatology. 1990 Jun;11(6):975-81. doi: 10.1002/hep.1840110611.
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 alpha-ketoacid dehydrogenase complex and the alpha-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 alpha-ketoglutarate dehydrogenase complex. Seventy-three of 188 (39%) primary biliary cirrhosis sera reacted with alpha-ketoglutarate dehydrogenase complex-E2 when immunoblotted against purified alpha-ketoglutarate dehydrogenase complex; one of these sera also reacted with the E1 component. In addition, primary biliary cirrhosis sera possessing alpha-ketoglutarate dehydrogenase complex-E2 reactivity specifically inhibited enzyme function of alpha-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 alpha-ketoacid dehydrogenase complex-E2, which lacked alpha-ketoglutarate dehydrogenase complex-E2 reactivity. Furthermore, affinity-purified primary biliary cirrhosis sera against alpha-ketoglutarate dehydrogenase complex-E2 inhibited only alpha-ketoglutarate dehydrogenase complex activity but did not alter enzyme activity of either pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex. Finally, alpha-ketoglutarate dehydrogenase complex-E2 specific affinity-purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex.(ABSTRACT TRUNCATED AT 250 WORDS)
原发性胆汁性肝硬化患者的血清中含有可识别线粒体蛋白的自身抗体。现已确定其中五种靶自身抗原为三种相关多酶复合物的酶：丙酮酸脱氢酶复合物、支链α-酮酸脱氢酶复合物和α-酮戊二酸脱氢酶复合物。每种复合物都由称为E1、E2和E3的组成酶构成。在本报告中，我们证实原发性胆汁性肝硬化血清可与α-酮戊二酸脱氢酶复合物的E2组分二氢硫辛酰胺琥珀酰转移酶发生反应。当用纯化的α-酮戊二酸脱氢酶复合物进行免疫印迹时，188份原发性胆汁性肝硬化血清中有73份（39%）与α-酮戊二酸脱氢酶复合物-E2发生反应；其中一份血清还与E1组分发生反应。此外，具有α-酮戊二酸脱氢酶复合物-E2反应性的原发性胆汁性肝硬化血清可特异性抑制α-酮戊二酸脱氢酶复合物的酶功能。酶活性不受含有针对丙酮酸脱氢酶复合物-E2和/或支链α-酮酸脱氢酶复合物-E2自身抗体但缺乏α-酮戊二酸脱氢酶复合物-E2反应性的原发性胆汁性肝硬化血清的影响。此外，针对α-酮戊二酸脱氢酶复合物-E2亲和纯化的原发性胆汁性肝硬化血清仅抑制α-酮戊二酸脱氢酶复合物的活性，但不改变丙酮酸脱氢酶复合物或支链α-酮酸脱氢酶复合物的酶活性。最后，α-酮戊二酸脱氢酶复合物-E2特异性亲和纯化抗血清在免疫印迹上不与丙酮酸脱氢酶复合物或支链α-酮酸脱氢酶复合物的任何组成酶发生反应。（摘要截短于250字）
