Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?

Patrick S C Leung, Kit Lam, Mark J Kurth, Ross Leon Coppel, M Eric Gershwin

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)577 - 582
Number of pages6
JournalTrends in Molecular Medicine
Volume18
Issue number10
DOIs
Publication statusPublished - 2012

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