Format

Send to:

Choose Destination
See comment in PubMed Commons below
Trends Mol Med. 2012 Oct;18(10):577-82. doi: 10.1016/j.molmed.2012.07.005. Epub 2012 Aug 21.

Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?

Author information

  • 1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA. psleung@ucdavis.edu

Abstract

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.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
22920894
[PubMed - indexed for MEDLINE]
PMCID:
PMC3465509
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk