Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis
Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis
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DOI：
10.1097/00008571-199706000-00002
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发表时间：
1997-06-01
期刊：
影响因子：
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通讯作者：
Beaune, PH
中科院分区：
文献类型：
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作者：
Belloc, C;Gauffre, A;Beaune, PH
双肼屈嗪诱导的自身免疫性肝炎患者血清中存在抗肝微粒体（LM）自身抗体，参与双肼屈嗪代谢的细胞色素P450 1A 2（CYP 1A 2）被证明是自身抗体的靶点。由于抗LM自身抗体对CYP 1A 2的特异性已被确定，因此进一步定位了其抗原位点。通过构建CYP 1A 2 cDNA片段，并用几种抗LM血清探测相应的蛋白，我们能够确定与100%血清免疫反应的区域（氨基酸335-471），该区域的内部缺失导致抗LM自身抗体识别的丧失，证实了表位是构象的。先前已对CYP 2D 6、CYP 17、CYP 21 A2进行了表位作图研究，最近对CYP 3A 1和CYP 2C 9进行了表位作图研究。将这些数据与本研究中获得的CYP 1A 2结果进行比较。
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.