Cytochrome P450 2D6 (LKM 1)
Diseases:
Autoimmune Hepatitis Type II
Cytochrome P450 2D6 is a member of a complex family of microsomal enzymes (mono-oxygenases) present in the endoplasmic reticulum membrane, which perform detoxification reaction on xenobiotic compounds. Cytochrome P450 2D6 is the molecular target of autoantibodies against the "liver kidney microsomal antigen 1" (LKM 1) which has been classically defined by immunofluorescence microscopy. The presence of these autoantibodies is considered indicative of autoimmune hepatitis type 2; LKM 1 antibodies have also been detected in patients with hepatitis C viral infection. The International Autoimmune Hepatitis Group therefore has subdivided the AIH type 2 into two subgroups: 2a with HCV and 2b without HCV. AIH 2a patients are often over 40 and predominantly male.
Cytochrome P450 2D6 from DIARECT is expressed as a full-length molecule in the baculovirus expression system.
The use of a purified recombinant Cytochrome P450 2D6 antigen allows the differentiation of autoimmune hepatitis from drug-induced hepatitis where transient autoantibodies to other P450 family members occur which cannot be differentiated by immunofluorescence techniques.
相关疾病:自身免疫性肝炎II型
自身免疫性肝炎(AIH)是一种病因不明并且对肝薄壁组织逐渐损害的紊乱性疾病。如果不进行治疗会有很高的死亡率。该疾病的特点之一是在大约90%以上患该病的患者血清中可检出自身抗体。从临床和血清学角度,把AIH病人分为两种不同的类型。Ⅰ型的特点是在AIH患者血清中可检测到抗平滑肌抗体和/或抗核酸抗体,Ⅱ型的病人可检测出抗肝肾微粒体1型抗体(LKM1)和抗肝细胞胞质1型抗体(LC1)。
LC1自身抗体在10%的AIH病人血清中可检测到,可作为一种血清学标记物。
细胞色素P450 2D6是微粒体酶(单氧化酶)复合体家族中的一员,位于内质网膜上,在外来复合物上起解毒作用。通过免疫荧光显微技术,发现细胞色素P450 2D6是肝肾微粒体酶抗原1(LKM1)的自身抗体的分子靶标。这种自身抗体被认为对自身免疫肝炎2型疾病有指示作用;LKM1抗体也在丙型病毒性肝炎患者的血清中被检测到。所以,国际上又将自身免疫肝炎2型(AIH type 2)分为两个亚型:2a,无HCV;2b,有HCV。AIH 2a患者通常在儿童期发病,AIH 2b型患者年龄通常大于40岁,且主要是男性。
DIARECT生产的细胞色素P450 2D6是在杆状病毒表达系统中表达的全长蛋白。
纯化的重组细胞色素P450 2D6抗原的使用,使药物诱发的自身免疫肝炎得以被鉴别,而抗其他P450家族的暂时性自身抗体不能通过免疫荧光技术鉴别。