Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?
- Authors
- Type
- Published Article
- Journal
- Trends in Molecular Medicine
- Publisher
- Elsevier
- Volume
- 18
- Issue
- 10
- Pages
- 577–582
- Identifiers
- DOI: 10.1016/j.molmed.2012.07.005
- Source
- Kit Lam Lab
- License
- Unknown
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.
