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中间型链球菌组蛋白样DNA结合蛋白在原发性胆汁性肝硬化胆管损伤发病机制中的可能作用

A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis.

作者信息

Haruta Ikuko, Kikuchi Ken, Hashimoto Etsuko, Kato Hidehito, Hirota Katsuhiko, Kobayashi Makio, Miyake Yoichiro, Uchiyama Takehiko, Yagi Junji, Shiratori Keiko

机构信息

Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Japan.

出版信息

Clin Immunol. 2008 May;127(2):245-51. doi: 10.1016/j.clim.2008.01.010. Epub 2008 Mar 11.

DOI:10.1016/j.clim.2008.01.010
PMID:18337173
Abstract

Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). It was reported that anti-histone autoantibody was detected in PBC, suggesting that bacterial histone-like DNA-binding protein (HLP) may be involved in the pathogenesis of PBC. To identify bacterial species in PBC to confirm this possibility, serum reactivity to bacterial cells was studied by ELISA. The IgM class Streptococcus intermedius titers were significantly higher in PBC than chronic hepatitis due to hepatitis C virus (CH-C) and healthy subjects. Among the streptococci, S. intermedius was selected for further study. The antigenic peptide of S. intermedius of HLP was synthesized to examine the serum reactivity to Si-HLP. IgM class anti-Si-HLP peptide titers were significantly higher in PBC. Immunoreactivity to anti-Si-HLP was detected in the cytoplasm of biliary epithelial cells and inflammatory cells in the portal area in PBC patients' livers. Streptococci, especially S. intermedius, might play a key role in the pathogenesis of PBC, possibly involving HLP.

摘要

细菌感染已成为原发性胆汁性肝硬化(PBC)发病机制中的一个关注焦点。据报道,在PBC中检测到抗组蛋白自身抗体,这表明细菌类组蛋白DNA结合蛋白(HLP)可能参与PBC的发病机制。为了鉴定PBC中的细菌种类以证实这种可能性,通过酶联免疫吸附测定(ELISA)研究了血清对细菌细胞的反应性。与丙型肝炎病毒引起的慢性肝炎(CH-C)和健康受试者相比,PBC中IgM类中间链球菌滴度显著更高。在链球菌中,选择中间链球菌进行进一步研究。合成了中间链球菌HLP的抗原肽,以检测血清对Si-HLP的反应性。PBC中IgM类抗Si-HLP肽滴度显著更高。在PBC患者肝脏的胆管上皮细胞和门管区炎症细胞的细胞质中检测到了对抗Si-HLP的免疫反应性。链球菌,尤其是中间链球菌,可能在PBC的发病机制中起关键作用,可能涉及HLP。

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