Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis
Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis
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DOI：
10.1016/s0168-8278(03)00501-4
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发表时间：
2004-01-01
影响因子：
25.7
通讯作者：
Vergani, D
中科院分区：
文献类型：
--
作者：
Bogdanos, DP;Baum, H;Vergani, D
背景/目标：先前对原发性胆汁性肝硬化（PBC）患者的研究表明，人丙酮酸脱氢酶复合物-E2（PDC-E2）的优势B和T细胞表位与微生物模拟物之间存在广泛的交叉反应性。这些观察结果表明，微生物感染通过分子模拟机制在诱导抗线粒体抗体中发挥作用。方法：通过查询蛋白质数据库，在大肠杆菌、幽门螺杆菌、铜绿假单胞菌、巨细胞病毒和流感嗜血杆菌中发现10个与PDC-E2高度相似的非PDC-E2微生物序列（212-226）。我们报告了一项研究测试反应性和竞争性交叉反应性对这些各自的肽，在某些情况下，父母的蛋白质，从55例PBC患者的血清，190例病理和28例健康对照的反应性相比。大肠杆菌模拟物常见于PBC和病理对照的子集中，除了没有证据表明尿路感染和与抗线粒体反应性相关的地方。coli/PDC-E2交叉反应性免疫是原发性胆汁性肝硬化的特征;大肠杆菌免疫原性模拟物可能是主要PDC-E2自身表位占优势的原因。(C)2003年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Previous studies on patients with primary biliary cirrhosis (PBC) have shown extensive cross-reactivity between the dominant B- and T-cell epitopes of human pyruvate dehydrogenase complex-E2 (PDC-E2), and microbial mimics. Such observations have suggested microbial infection as having a role in the induction of anti-mitochondrial antibodies, through a mechanism of molecular mimicry. However the biological significance of these cross-reactivities is questionable, because PDC-E2 is so highly conserved among various species.Methods: Interrogating protein databases, ten non-PDC-E2 microbial sequences with high degree of similarity to PDC-E2(212-226) were found in Escherichia coli (6), Helicobacter pylori, Pseudomonas aeruginosa, Cytomegalovirus, and Haemophilus influenzae. We report on a study testing reactivity and competitive cross-reactivity against these respective peptides, and in some cases the parent protein, using sera from 55 patients with PBC, compared to reactivity of 190 pathological and 28 healthy controls.Results: Cross-reactivity to E. coli mimics was commonly seen in PBC, and in a subset of pathological controls except where there was no evidence of urinary tract infection and correlated with anti-mitochondrial reactivity.Conclusions: E. coli/PDC-E2 cross-reactive immunity characterizes primary biliary cirrhosis; the large number of E. coli immunogenic mimics may account for the dominance of the major PDC-E2 autoepitope. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.