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 language | English (US) |
|---|---|
| Pages (from-to) | 577-582 |
| Number of pages | 6 |
| Journal | Trends in Molecular Medicine |
| Volume | 18 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2012 |
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ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
Cite this
Xenobiotics and autoimmunity : Does acetaminophen cause primary biliary cirrhosis? / Leung, Patrick S; Lam, Kit; Kurth, Mark J.; Coppel, Ross L.; Gershwin, M. Eric.
In: Trends in Molecular Medicine, Vol. 18, No. 10, 10.2012, p. 577-582.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Xenobiotics and autoimmunity
T2 - Does acetaminophen cause primary biliary cirrhosis?
AU - Leung, Patrick S
AU - Lam, Kit
AU - Kurth, Mark J.
AU - Coppel, Ross L.
AU - Gershwin, M. Eric
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molmed.2012.07.005
DO - 10.1016/j.molmed.2012.07.005
M3 - Article
VL - 18
SP - 577
EP - 582
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 10
ER -