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首页> 外文期刊>Autoimmunity >Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C.
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Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C.

机译：自身免疫性肝炎，慢性乙型肝炎和慢性丙型肝炎患者血清对多种人类细胞色素P450蛋白的免疫反应性。

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Numerous human Cytochrome P450 enzymes (CYPs) associated with 'phase I' drug metabolism have been identified. Among them, CYP2D6 is thought to be the major target autoantigen to anti-liver kidney microsome (LKM)-1 autoantibody, a characteristic feature of autoimmune hepatitis (AIH) type II. In this study, we were able to clone CYP2D6 cDNA from a human liver cDNA library and express the CYP2D6 recombinant protein, and also to prepare four other representative human CYP proteins (CYP1A2, 2C9, 2E1, and 3A4). These preparations were used to assay the immunoreactivity of patients with AIH type I (n=35) and type II (n=9). As comparison groups, sera from patients with chronic hepatitis B (n=15), chronic hepatitis C (n=55; 24 anti-LKM-1-positive, 31 anti-LKM-1-negative), and from normal controls (n=30) were included. The five CYP proteins did not react with sera from normal controls nor from patients with chronic hepatitis B. CYP2D6 reacted with sera from 100% (9/9) of AIH type II patients, 79% (19/24) of patients with anti-LKM-1-positive chronic hepatitis C, and 6.5% (2/31) of patients with anti-LKM-1-negative chronic hepatitis C. In contrast, CYP1A2 reacted with serum from one patient with AIH type I, CYP2E1 reacted with sera from two patients with AIH type I, one patient with anti-LKM-1-positive chronic hepatitis C, and two patients with anti-LKM-1-negative chronic hepatitis C, and CYP3A4 reacted with sera from one patient with AIH type II and one patient with anti-LKM-1-positive chronic hepatitis C. CYP2C9 did not react with any of the sera included in this study. From these results, it is suggested that CYPs other than CYP2D6 can function as immunotargets in certain disease conditions.
机译：已经确定了与“ I期”药物代谢有关的多种人类细胞色素P450酶（CYP）。其中，CYP2D6被认为是抗肝肾微粒体（LKM）-1自身抗体的主要靶标自身抗原，II型是自身免疫性肝炎（AIH）的特征。在这项研究中，我们能够从人肝cDNA文库中克隆CYP2D6 cDNA并表达CYP2D6重组蛋白，还能够制备其他四种代表性的人CYP蛋白（CYP1A2、2C9、2E1和3A4）。这些制剂用于测定I型AIH（n = 35）和II型AIH（n = 9）患者的免疫反应性。作为比较组，来自慢性乙型肝炎（n = 15），慢性丙型肝炎（n = 55; 24名抗LKM-1阳性，31名抗LKM-1阴性）和正常对照组（n = 30）。这五种CYP蛋白与正常对照组或慢性乙型肝炎患者的血清均不发生反应。CYP2D6与100％（9/9）的II型AIH患者，79％（19/24）的抗HBV患者的血清发生反应LKM-1阳性慢性丙型肝炎，以及抗LKM-1阴性慢性丙型肝炎患者的6.5％（2/31）。相比之下，CYP1A2与一名AIH I型患者的血清反应，CYP2E1与血清反应来自两名I型AIH患者，一名抗LKM-1阳性慢性丙型肝炎患者，两名抗LKM-1阴性慢性丙型肝炎患者和CYP3A4与一名AIH II型患者的血清反应。一名抗LKM-1阳性的慢性丙型肝炎患者。CYP2C9对本研究包括的任何血清均无反应。从这些结果表明，在某些疾病条件下，CYP2D6以外的CYP可以作为免疫靶标。

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