Antibodies against mitochondrial dehydrogenase complexes in primary biliary cirrhosis.
Antibodies against mitochondrial dehydrogenase complexes in primary biliary cirrhosis.
复制标题
原发性胆汁性肝硬化中线粒体脱氢酶复合物的抗体。
DOI：
10.1016/0016-5085(90)91247-4
复制
发表时间：
1990
期刊：
影响因子：
29.4
通讯作者：
Danner,D
中科院分区：
文献类型：
--
作者：
Yoshida,T;Bonkovsky,H;Ansari,A;Danner,D
抗线粒体抗体是原发性胆汁性肝硬化的血清学标志，最近发现抗线粒体抗体针对线粒体脱氢酶复合物（丙酮酸、支链酮酸和α-酮戊二酸脱氢酶）的E2亚单位。本研究的目的是扩展这些发现，并确定是否从原发性胆汁性肝硬化患者的血清中纯化的免疫球蛋白抑制这些脱氢酶复合物在体外的活性。检测了14例原发性胆汁性肝硬化患者（13例线粒体抗体阳性）、23例风湿性疾病患者和30例慢性活动性肝炎患者（间接免疫荧光法检测全部53例线粒体抗体阳性）、10例酒精性肝病患者和5例正常对照的血清。免疫印迹法检测丙酮酸脱氢酶、支链α-酮酸脱氢酶和α-酮戊二酸脱氢酶复合物抗体，酶联免疫吸附试验定量。在14例原发性胆汁性肝硬化患者的血清样本中，丙酮酸、支链酮酸和α-酮戊二酸脱氢酶的E2亚单位分别有13、11和2例样本经免疫印迹检测呈阳性。相反，来自风湿性疾病、慢性活动性肝炎和酒精性肝病受试者以及对照受试者的样本对这些抗体检测为阴性。具有高滴度的线粒体抗体的血清免疫球蛋白G表现出浓度依赖性的脱氢酶复合物的活性抑制，并且观察到对丙酮酸脱氢酶复合物的抑制活性与免疫球蛋白对该复合物的倒数滴度之间的密切相关性（r = 0.917，n = 13）。这些数据表明，这种自身抗体，除了作为原发性胆汁性肝硬化的诊断标志物，可能有一个致病的作用，他们的能力，抑制重要的线粒体酶。
Antimitochondrial antibodies, serological hallmarks of primary biliary cirrhosis, recently were found to be directed against the E2 subunits of mitochondrial dehydrogenase complexes (pyruvate, branchedchain ketoacid, and α-ketoglutarate dehydrogenases). The objectives of this study were to extend these findings and to determine whether purified immunoglobulin from the sera of patients with primary biliary cirrhosis inhibit activity of these dehydrogenase complexes in vitro. Sera were examined from 14 patients with primary biliary cirrhosis (13 mitochondrial antibody positive), 23 with rheumatic diseases and 30 with chronic active hepatitis (all 53 positive for mitochondrial antibodies by indirect immunofluorescence), 10 with alcoholic liver disease, and 5 normal controls. Antibodies against pyruvate dehydrogenase, branched-chain α-ketoacid dehydrogenase and α-ketoglutarate dehydrogenase complexes were detected by immunoblot and quantified by enzyme-linked immunosorbent assay. Of the 14 serum samples obtained from patients with primary biliary cirrhosis, 13, 11, and 2 samples tested positive by immunoblot for the E2 subunits of pyruvate, branched-chain ketoacid, and α-ketoglutarate dehydrogenase, respectively. In contrast, samples from subjects with rheumatic diseases, chronic active hepatitis, and alcoholic liver disease and control subjects tested negative for these antibodies. Serum immunoglobulin G with high titers of mitochondrial antibodies showed concentration-dependent inhibition of activity of the dehydrogenase complexes, and close correlation (r = 0.917, n = 13) was observed between inhibitory activity against pyruvate dehydrogenase complex and the reciprocal titer of immunoglobulin against this complex. These data suggest that such autoantibodies, besides serving as diagnostic markers for primary biliary cirrhosis, may have a pathogenic role by their ability to inhibit important mitochondrial enzymes.