Document Detail


Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?
MedLine Citation:
PMID:  22920894     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The serologic hallmark of primary biliary cirrhosis (PBC) is the presence of antimitochondrial autoantibodies (AMAs) directed against the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). The PBC-related autoepitope of PDC-E2 contains lipoic acid, and previous work has demonstrated that mimics of lipoic acid following immunization of mice lead to a PBC-like disease. Furthermore, approximately one-third of patients who have ingested excessive amounts of acetaminophen (paracetamol) develop AMA of the same specificity as patients with PBC. Quantitative structure-activity relationship (QSAR) data indicates that acetaminophen metabolites are particularly immunoreactive with AMA, and we submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate a loss of tolerance and lead to the development of PBC.
Authors:
Patrick S C Leung; Kit Lam; Mark J Kurth; Ross L Coppel; M Eric Gershwin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-21
Journal Detail:
Title:  Trends in molecular medicine     Volume:  18     ISSN:  1471-499X     ISO Abbreviation:  Trends Mol Med     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-05     Completed Date:  2013-02-15     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100966035     Medline TA:  Trends Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  577-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA. psleung@ucdavis.edu
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / administration & dosage,  adverse effects*,  immunology
Animals
Autoantibodies / immunology
Autoimmunity*
Humans
Liver Cirrhosis, Biliary / chemically induced*,  immunology
Mice
Mitochondria / drug effects,  metabolism
Pyruvate Dehydrogenase Complex / metabolism
Quantitative Structure-Activity Relationship
Thioctic Acid / metabolism
Xenobiotics / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
DK067003/DK/NIDDK NIH HHS; DK39588/DK/NIDDK NIH HHS; R01 DK039588/DK/NIDDK NIH HHS; R01 DK067003/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Pyruvate Dehydrogenase Complex; 0/Xenobiotics; 103-90-2/Acetaminophen; 62-46-4/Thioctic Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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