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Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis
1Department of Pharmacology and Toxicology, Imperial College School of Medicine at St. Mary's, London, UK. erieli@ki.se
Molecular Pharmacology
|September 1, 1996
Summary
Autoantibodies targeting cytochrome P450 2E1 (CYP2E1) are linked to halothane hepatitis. These antibodies recognize trifluoroacetylated CYP2E1, potentially explaining the immune response in this liver condition.
Area of Science:
- Hepatology
- Immunology
- Biochemistry
Background:
- Cytochrome P450 2E1 (CYP2E1) catalyzes the formation of trifluoroacetylated proteins.
- These modified proteins are implicated as target antigens in halothane hepatitis.
Purpose of the Study:
- To investigate the role of CYP2E1 and its modification in halothane hepatitis.
- To determine if autoantibodies against CYP2E1 are present in patients with halothane hepatitis.
Main Methods:
- Detection of trifluoroacetylated CYP2E1 in rat livers using halothane treatment.
- Enzyme-linked immunosorbent assay (ELISA) to detect autoantibodies against CYP2E1 in patient sera.
- Immunofluorescence and immunoprecipitation to study the cellular distribution of adducts and CYP2E1.
Main Results:
- Trifluoroacetylated CYP2E1 was detected in halothane-treated rat livers.
- High levels of autoantibodies recognizing CYP2E1 were found in 70% of halothane hepatitis patients' sera.
- These antibodies were largely absent in healthy controls and patients without halothane hepatitis.
- Trifluoroacetylated adducts and CYP2E1 were found in the endoplasmic reticulum and on the cell surface of rat hepatoma cells.
Conclusions:
- Immune responses targeting cell surface CYP2E1 may contribute to the pathogenesis of halothane hepatitis.
- CYP2E1 is a likely target antigen in halothane-induced liver injury.