Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis.

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Belloc C, Gauffre A, Andre C, Beaune PH

Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis.

Pharmacogenetics. 1997 Jun;7(3):181-6.

PubMed ID

9241657 [ View in PubMed

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Abstract

Dihydralazine-induced hepatitis is characterized by the presence of anti-liver microsomal (anti-LM) autoantibodies in the sera of patients. Cytochrome P450 1A2 (CYP1A2), involved in the metabolism of dihydralazine, was shown to be a target for autoantibodies. In order to investigate further the relationship between drug metabolism and the pathogenesis of this drug-induced autoimmune disease, and since the specificity of anti-LM autoantibodies towards CYP1A2 has been determined, the antigenic site was further localized. By constructing fragments derived from CYP1A2 cDNA and probing the corresponding proteins with several anti-LM sera, we were able to define a region (amino acid 335-471) which was immunoreactive with 100% of sera. An internal deletion in this region led to the loss of recognition by anti-LM autoantibodies, confirming that the epitope was conformational. Epitope mapping studies had previously been performed for CYP2D6, CYP17, CYP21A2, and recently for CYP3A1 and CYP2C9. Those data were compared with results obtained in the present study for CYP1A2.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dihydralazine	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details