Xenobiotics and loss of tolerance in primary biliary cholangitis

查看全文 作　　者：Jinjun [1,2]Wang;Guoxiang [1]Yang;Alana Mari [1]Dubrovsky;Jinjung [1]Choi;Patrick SC [1]Leung

机构地区：[1]Division of Rheumatology,Allergy and Clinical Immunology,University of California at Davis,School of Medicine;[2]College of Environmental Science and Engineering,Yangzhou University

出　　处：《World Journal of Gastroenterology》索引2016年第22卷第1期,共11页

基　　金：Supported by National Institutes of Health grants (in part), DK39588, DK090019 and DK067003 摘　　要：Data from genome wide association studies and geoepidemiological studies established that a com-bination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis(PBC).The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies(AMA)that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2(PDC--E2)subunit.Extensive efforts have been directed to investigate the molecular basis of AMA.Recently,experimental data has pointed to the thesis that the breaking of tolerance to PDC--E2 is a pivotal event in the initial etiology of PBC,including environmental xenobiotics including those commonly found in cos-metics and food additives,suggesting that chemical modification of the PDC--E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts.Here,we will discuss the natural history,genetics and immunobiology of PBC and structural constraints of PDC--E2 in AMA recognition which makes it vulnerable to chemical modification. 关键词：Antimitochondrial AUTOANTIBODIES Primarybiliary CHOLANGITIS PYRUVATE DEHYDROGENASE E2 Breakingof TOLERANCE Xenobiotics

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Xenobiotics and loss of tolerance in primary biliary cholangitis

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