Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?

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

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15 Citations (Scopus)


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
Issue number10
Publication statusPublished - 2012

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