Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis

Mohammed Bourdi, Weiqiao Chen, Raimund M. Peter, Jackie L. Martin, Jeroen T M Buters, Sidney D. Nelson, Lance R. Pohl

Research output: Contribution to journalArticle

Abstract

Autoantibodies against specific human cytochrome P450s have been found in the sera of patients suffering from a variety of diseases, including those caused by drugs. In the cases of tienilic acid- and dihydralazine-induced hepatitis, patients have serum autoantibodies directed against cytochromes P450 2C9 and P450 1A2, respectively. In the present study, we have found that 25 of 56 (45%) patients diagnosed with halothane hepatitis have autoantibodies that react with human cytochrome P450 2E1 that was purified from a baculovirus expression system. The autoantibodies inhibited the activity of cytochrome P450 2E1 and appeared to be directed against mainly conformational epitopes. In addition, because cytochrome P450 2E1 became trifluoroacetylated when it oxidatively metabolized halothane, it is possible that the covalently altered form of cytochrome P450 2E1 may be able to bypass the immunologic tolerance that normally exists against cytochrome P450 2E1. A similar mechanism may explain the formation of autoantibodies that have been found against other cellular targets of the reactive trifluoroacetyl chloride metabolite of halothane.

Original languageEnglish (US)
Pages (from-to)1159-1166
Number of pages8
JournalChemical Research in Toxicology
Volume9
Issue number7
DOIs
StatePublished - 1996

Fingerprint

Cytochrome P-450 CYP2E1
Autoantigens
Halothane
Autoantibodies
Ticrynafen
Dihydralazine
Baculoviridae
Cytochromes
Metabolites
Serum
Cytochrome P-450 Enzyme System
Hepatitis
Epitopes
Halothane Hepatitis
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Bourdi, M., Chen, W., Peter, R. M., Martin, J. L., Buters, J. T. M., Nelson, S. D., & Pohl, L. R. (1996). Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chemical Research in Toxicology, 9(7), 1159-1166. https://doi.org/10.1021/tx960083q

Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. / Bourdi, Mohammed; Chen, Weiqiao; Peter, Raimund M.; Martin, Jackie L.; Buters, Jeroen T M; Nelson, Sidney D.; Pohl, Lance R.

In: Chemical Research in Toxicology, Vol. 9, No. 7, 1996, p. 1159-1166.

Research output: Contribution to journalArticle

Bourdi, M, Chen, W, Peter, RM, Martin, JL, Buters, JTM, Nelson, SD & Pohl, LR 1996, 'Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis', Chemical Research in Toxicology, vol. 9, no. 7, pp. 1159-1166. https://doi.org/10.1021/tx960083q
Bourdi, Mohammed ; Chen, Weiqiao ; Peter, Raimund M. ; Martin, Jackie L. ; Buters, Jeroen T M ; Nelson, Sidney D. ; Pohl, Lance R. / Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. In: Chemical Research in Toxicology. 1996 ; Vol. 9, No. 7. pp. 1159-1166.
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