Joplin R E, Neuberger J M
Liver Research Laboratories, University Hospital Birmingham, UK.
Eur J Gastroenterol Hepatol. 1999 Jun;11(6):587-93. doi: 10.1097/00042737-199906000-00002.
A major advance in the study of primary biliary cirrhosis was identification of the major B-cell auto-antigen as the mitochondrial enzyme pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2). Subsequent studies revealed that PDC-E2 also contained epitopes recognized by patients' T cells. Furthermore, aberrant expression of MHC class II, intercellular adhesion molecules, lymphocyte co-stimulatory molecules and B-cell epitopes of PDC-E2 was observed on patients' biliary epithelium, supporting the concept that biliary epithelial cells are the target of a focused autoimmune reaction. Changes in distribution of auto-antigen on biliary epithelium and the presence of auto-antibody in patient's serum have both been shown to occur very early in the natural history of primary biliary cirrhosis, suggesting an intimate role for these molecules in immunopathogenetic mechanisms.
原发性胆汁性肝硬化研究中的一项重大进展是，将主要的B细胞自身抗原鉴定为线粒体酶丙酮酸脱氢酶二氢硫辛酰胺乙酰转移酶（PDC-E2）。随后的研究表明，PDC-E2还包含患者T细胞识别的表位。此外，在患者的胆管上皮细胞上观察到MHC II类分子、细胞间黏附分子、淋巴细胞共刺激分子以及PDC-E2的B细胞表位的异常表达，这支持了胆管上皮细胞是局部自身免疫反应靶点的概念。胆管上皮细胞上自身抗原分布的变化以及患者血清中自身抗体的存在均已被证明在原发性胆汁性肝硬化的自然病程中很早就会出现，这表明这些分子在免疫发病机制中发挥着密切作用。
