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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 338-348
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.338
Xenobiotics and loss of tolerance in primary biliary cholangitis
Jinjun Wang, Guoxiang Yang, Alana Mari Dubrovsky, Jinjung Choi, Patrick SC Leung
Jinjun Wang, Guoxiang Yang, Alana Mari Dubrovsky, Jinjung Choi, Patrick SC Leung, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, School of Medicine, Davis, CA 95616, United States
Jinjun Wang, College of Environmental Science and Engineering, Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Author contributions: Wang J, Yang G and Leung PSC contributed to the study design, literature search, manuscript writing and final revision of the manuscript; Dubrovsky AM and Choi J contributed to literature search and manuscript writing.
Supported by National Institutes of Health grants (in part), DK39588, DK090019 and DK067003.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Patrick SC Leung, PhD, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, United States. psleung@ucdavis.edu
Telephone: +1-530-7544943 Fax: +1-530-7546047
Received: April 30, 2015
Peer-review started: May 8, 2015
First decision: July 14, 2015
Revised: August 15, 2015
Accepted: December 1, 2015
Article in press: December 1, 2015
Published online: January 7, 2016
Core Tip

Core tip: Environment influences immune functions. In this paper, we examine how environmental chemicals can trigger autoimmunity in an organ specific autoimmune disease, primary biliary cholangitis (PBC). PBC is liver specific autoimmune disease characterized by high titer of anti-mitochondrial autoantibodies directed against the E2 subunit of pyruvate dehydrogenase (PDC-E2) lipoyl domain. Here, we present experimental evidence from quantitative structure-activity relationship and animal models that xenobiotic modification of the PDC-E2 lipoyl domain could lead to loss of self-tolerance and is a pivotal event in the initial etiology of PBC in genetically susceptible hosts.