Identification of cytochrome P450IA2 as a human autoantigen.
Identification of cytochrome P450IA2 as a human autoantigen.
复制标题
细胞色素 P450IA2 鉴定为人类自身抗原。
DOI：
10.1016/0003-9861(90)90541-6
复制
发表时间：
1990
影响因子：
3.9
通讯作者：
Johnson,EF
中科院分区：
文献类型：
--
作者：
Manns,MP;Griffin,KJ;Quattrochi,LC;Sacher,M;Thaler,H;Tukey,RH;Johnson,EF
发现发生在特发性自身免疫型慢性活动性肝炎（CAH）患者中的自身抗体与纯化的兔细胞色素P450 IA 2反应，与P450 IA 1反应的程度要小得多。这两种细胞色素P450是已知的诱导2，3，7，8-四氯二苯并-p-二恶英（TCDD）在兔子，和患者血清识别的微粒体蛋白的表达诱导成年兔肝脏后，与TCDD治疗。这种蛋白质仅在子宫内暴露于TCDD的新生兔的肝微粒体中微弱地检测到，这与TCDD对P450 IA 2的年龄依赖性诱导一致。该血清特异性地与从用含有全长人P450 IA 2 cDNA的表达载体转染的COS-1细胞制备的微粒体中类似大小的蛋白质反应。在单独用载体转染的细胞中未检测到这种反应性，表明抗体识别人P450 IA 2。此外，血清广泛抑制分离的人肝微粒体催化的7-乙氧基试卤灵O-脱乙基化。这种催化活性与其他物种中的IA类P450相关。对各种肝病和非肝病患者血清的筛选表明，CAH中很少出现P450 IA 2自身抗体。细胞色素P450 IA 2是第三个被鉴定为炎症性肝病自身抗原的P450。
Autoantibodies occurring in a patient with idiopathic autoimmune type chronic active hepatitis (CAH) were found to react with purified rabbit cytochrome P450IA2 and to a much lesser extent with P450IA1. Both cytochrome P450s are known to be inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rabbit, and the expression of the microsomal protein recognized by the patient serum was induced in adult rabbit livers after treatment with TCDD. This protein is only weakly detected in liver microsomes from neonatal rabbits exposed to TCDDin utero, which is consistent with the age-dependent induction of P450IA2 by TCDD. The serum specifically reacted with a protein of similar size in microsomes prepared from COS-1 cells transfected with an expression vector containing the full length human P450IA2 cDNA. This reactivity was not detected in the cells transfected with the vector alone, indicating that the antibody recognizes human P450IA2. In addition, the serum extensively inhibited 7-ethoxyresorufin O-deethylation catalyzed by isolated human liver microsomes. This catalytic activity is associated with class IA P450s in other species. A screen of sera from patients with various hepatic and nonhepatic diseases indicates that the autoantibody to P450IA2 occurs rarely in CAH. Cytochrome P450IA2 becomes the third P450 identified as an autoantigen in inflammatory liver diseases.