Flannery G R, Burroughs A K, Butler P, Chelliah J, Hamilton-Miller J, Brumfitt W, Baum H
Biochemistry Department, King's College London, United Kingdom.
Hepatology. 1989 Sep;10(3):370-4. doi: 10.1002/hep.1840100321.
Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common "M2 epitope" that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.
原发性胆汁性肝硬化患者的血清对线粒体表现出可变的自身抗体反应性，线粒体是最常见的抗原（命名为M2），包括三种分子量约为70、50和40kD的结构。这些抗原的性质直到最近才得以确定；70kD和50kD分别是丙酮酸脱氢酶复合体的转乙酰酶E2和组分X，且是不同的多肽。我们通过免疫印迹、抗体洗脱和再结合，证实了M2抗原主要条带之间明确的交叉反应性。此外，已显示与线粒体的三个M2条带中每条结合的抗体与革兰氏阴性菌和革兰氏阳性菌的两个主要抗原条带之间存在交叉反应性。相反，从大肠杆菌的这两条带洗脱的抗体被发现可结合线粒体的所有三个M2条带。这些结果表明，原发性胆汁性肝硬化的抗体既包含肽特异性抗体，也包含交叉反应性抗体，后者识别一个可能包括肽的非蛋白质成分的共同“M2表位”。然而，直接和竞争性酶联免疫吸附测定未能表明丙酮酸脱氢酶复合体的辅酶硫辛酸或其酰胺是共同的抗原部分。
