Autoantibodies in primary biliary cirrhosis: Recent progress in research on the pathogenetic and clinical significance
Autoantibodies in primary biliary cirrhosis: Recent progress in research on the pathogenetic and clinical significance
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DOI：
10.3748/wjg.v20.i10.2606
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发表时间：
2014-03-14
影响因子：
4.3
通讯作者：
Aoyagi, Yutaka
中科院分区：
文献类型：
--
作者：
Yamagiwa, Satoshi;Kamimura, Hiroteru;Aoyagi, Yutaka
原发性胆汁性肝硬化（PBC）是一种慢性进行性胆汁淤积性肝病，其特征是免疫介导的肝内中小型胆管破坏和血清中存在抗线粒体抗体（AMA）。AMA在超过90%的PBC患者中被检测到，而其在一般人群中的患病率极低，从0.16%到1%不等。以往的研究表明，胆管上皮细胞发生凋亡的独特特征可能导致对线粒体自身抗原的高度直接和非常特异的免疫反应。此外，最近的研究表明，AMA阳性PBC患者的血清与丙酮酸脱氢酶复合物的许多异生物质修饰的E2亚单位反应，这在正常个体的血清中未观察到。这些发现表明，来自环境的化学物质可能与线粒体自身抗原耐受性的破坏有关。虽然目前普遍认为AMA是PBC最特异的血清学标志物，但已在PBC患者中研究了超过60种自身抗体，其中一些先前被认为对其他自身免疫性疾病具有特异性。本文就PBC中重要自身抗体的发病机制及临床意义的研究进展作一综述。确定这些自身抗体在PBC中的致病作用仍然是基础和临床研究的优先事项。(C)2014百世登出版集团有限公司有限公司All rights reserved.
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMA) in the serum. AMA are detected in over 90% of patients with PBC, whereas their prevalence in the general population is extremely low, varying from 0.16% to 1%. Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens. Moreover, recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 sub-units of the pyruvate dehydrogenase complex, which is not observed in the serum of normal individuals. These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens. While it is currently generally accepted that AMA are the most specific serological markers of PBC, more than 60 autoantibodies have been investigated in patients with PBC, and some have previously been considered specific to other autoimmune diseases. This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC. Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.