Björkland A, Tötterman T H
Dept. of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
Scand J Gastroenterol Suppl. 1994;204:32-9. doi: 10.3109/00365529409103623.
This review summarizes the experimental and clinical support for an autoimmune origin of primary biliary cirrhosis (PBC). Direct proof is lacking, but indications in favour of an immunologic destructive mechanism include the demonstration of antibodies and T cell clones with specificity for mitochondrial autoantigens, and the lymphocytic infiltration/destruction of small bile ducts similar to that of graft-vs-host disease and rejection. There is a weak association with other autoimmune diseases, but no clear HLA linkage. Spontaneous animal models for PBC are lacking, and immunization of animals with purified autoantigen does not result in typical disease. Anti-mitochondrial antibodies (AMAs) of M2 type are diagnostic of PBC, and are mainly directed against a functional, restricted epitope on the E2 subunit of the pyruvate dehydrogenase complex (PDC). PDC-E2 shows several similarities to other classical autoantigens. The pathogenic role of AMA remains elusive. Recent studies have shown that AMAs detect an antigenic epitope expressed on the luminal surface of biliary epithelium in PBC liver. The initial triggering event might represent a microbial infection (molecular mimicry), or an aberrant surface expression of a true autoepitope.
本综述总结了原发性胆汁性肝硬化（PBC）自身免疫起源的实验和临床依据。虽然缺乏直接证据，但支持免疫破坏机制的迹象包括：存在对线粒体自身抗原具有特异性的抗体和T细胞克隆，以及小胆管的淋巴细胞浸润/破坏，这与移植物抗宿主病和排斥反应类似。PBC与其他自身免疫性疾病存在较弱的关联，但没有明确的HLA连锁关系。缺乏PBC的自发动物模型，用纯化自身抗原免疫动物也不会导致典型疾病。M2型抗线粒体抗体（AMA）是PBC的诊断标志物，主要针对丙酮酸脱氢酶复合体（PDC）E2亚基上一个功能性、受限的表位。PDC-E2与其他经典自身抗原有若干相似之处。AMA的致病作用仍不明确。最近的研究表明，AMA可检测到PBC肝脏中胆管上皮腔面表达的一个抗原表位。最初的触发事件可能是微生物感染（分子模拟），或者是真正自身表位的异常表面表达。
