EPITOPE MAPPING OF HUMAN CYP1A2 IN DIHYDRALAZINE-INDUCED AUTOIMMUNE HEPATITIS

Dihydralazine-induced hepatitis is characterized by the presence of an ti-liver microsomal (anti-LM) autoantibodies in the sera of patients, Cytochrome P450 1A2 (CYP1A2), involved in the metabolism of dihydralaz ine, was shown to be a target for autoantibodies, In order to investig ate further the relationship between drug metabolism and the pathogene sis of this drug-induced autoimmune disease, and since the specificity of anti-LM autoantibodies towards CYP1A2 has been determined, the ant igenic site was further localized, By constructing fragments derived f rom CYP1A2 cDNA and probing the corresponding proteins with several an ti-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 re gion led to the loss of recognition by anti-LM autoantibodies, confirm ing that the epitope was conformational. Epitope mapping studies had p reviously been performed for CYP2D6, CYP17, CYP21A2, and recently for CYP3A1 and CYP2C9. Those data were compared with results obtained in t he present study for CYP1A2.