Manns M P, Obermayer-Straub P
Department of Gastroenterology and Hepatology, Medizinische Hoschschule Hannover, Germany.
J Viral Hepat. 1997;4 Suppl 2:42-7. doi: 10.1111/j.1365-2893.1997.tb00179.x.
Autoimmunity may be observed in chronic viral hepatitis, in particular hepatitis C and D. The hepatitis C virus (HCV) displays numerous interactions with the immune system. Hepatitis C virus induces a number of diseases of presumed autoimmune background, like mixed cryoglobulinaemia, glomerulonephritis, panarthritis, arthritis, thyroiditis and skin lesions. On the other hand a number of autoantibodies are observed during the course of hepatitis C. Of particular interest are liver/kidney microsomal antibodies (LKM). Their occurrence in viral hepatitis may indicate an increased risk for treatment with interferons. LKM antibodies in chronic hepatitis C recognize several autoepitopes differing from those in autoimmune hepatitis. Hepatitis C-associated LKM antibodies are more heterogeneous. They recognize either conformational or several distinct linear autoepitopes on cytochrome P450 2D6; they may also react with other microsomal proteins. Apart from their molecular weight at 59 and 70 kDa these microsomal antigens are not yet identified. Another model of virus-induced autoimmunity in man is chronic hepatitis D which always requires co-infection with hepatitis B. Hepatitis D is known to be associated with a number of autoantibodies, amongst them LKM-3. LKM-3 antibodies have recently been shown to react with proteins of the UDP glucuronosyltransferase family (UGT). The main antigen is an autoepitope expressed on exon 2-5 of family 1 UGTs. Some hepatitis D sera recognize a minor second epitope on family 2 UGTs. It is interesting that hepatitis C patients recognize proteins of the cytochrome P450 family while hepatitis D sera react with UGTs. There seems to be little overlap between autoimmunity seen in hepatitis C and D as far as autoepitopes are concerned. LKM-3 antibodies against UGT 1 are also seen in a minority of patients with autoimmune hepatitis type 2. However, the autoimmune response against UGTs seen in autoimmune hepatitis differs from that observed in viral hepatitis. Autoantibodies in autoimmune liver disease are usually more homogenous and are directed against precise linear epitopes. Autoepitopes in autoimmune hepatitis usually represent conserved regions of these proteins, the antibody usually is inhibitory and antibody titres are very high. In contrast, autoantibodies in viral hepatitis are more heterogenous, recognize several linear and conformational epitopes; antibody titres are much lower. However, the major LKM autoantigen in chronic hepatitis C also is P450 2D6. Autoimmune hepatitis and autoimmunity in viral hepatitis must be distinguished clinically by all means due to the need for specific therapeutic interventions. These liver diseases may serve as models to study virus induced autoimmunity and autoimmune disease in man.
自身免疫现象可见于慢性病毒性肝炎，尤其是丙型和丁型肝炎。丙型肝炎病毒（HCV）与免疫系统存在着众多相互作用。丙型肝炎病毒可引发多种推测具有自身免疫背景的疾病，如混合性冷球蛋白血症、肾小球肾炎、全身性关节炎、关节炎、甲状腺炎及皮肤病变。另一方面，在丙型肝炎病程中可观察到多种自身抗体。特别值得关注的是肝肾微粒体抗体（LKM）。它们在病毒性肝炎中的出现可能提示使用干扰素治疗时风险增加。慢性丙型肝炎中的LKM抗体识别的几种自身表位与自身免疫性肝炎中的不同。丙型肝炎相关的LKM抗体更为异质性。它们识别细胞色素P450 2D6上的构象性或几种不同的线性自身表位；它们也可能与其他微粒体蛋白发生反应。除了分子量分别为59 kDa和70 kDa外，这些微粒体抗原尚未明确。人类病毒诱导自身免疫的另一个模型是慢性丁型肝炎，它总是需要与乙型肝炎合并感染。已知丁型肝炎与多种自身抗体有关，其中包括LKM - 3。最近发现LKM - 3抗体可与尿苷二磷酸葡萄糖醛酸转移酶家族（UGT）的蛋白发生反应。主要抗原是1型UGT家族外显子2 - 5上表达的一个自身表位。一些丁型肝炎血清可识别2型UGT家族上一个次要的第二表位。有趣的是，丙型肝炎患者识别细胞色素P450家族的蛋白，而丁型肝炎血清与UGT发生反应。就自身表位而言，丙型和丁型肝炎中的自身免疫现象似乎几乎没有重叠。少数2型自身免疫性肝炎患者也可出现针对UGT 1的LKM - 3抗体。然而，自身免疫性肝炎中针对UGT的自身免疫反应与病毒性肝炎中观察到的不同。自身免疫性肝病中的自身抗体通常更为均一，且针对精确的线性表位。自身免疫性肝炎中的自身表位通常代表这些蛋白的保守区域，抗体通常具有抑制作用且抗体滴度非常高。相比之下，病毒性肝炎中的自身抗体更为异质性，识别几种线性和构象性表位；抗体滴度要低得多。然而，慢性丙型肝炎中的主要LKM自身抗原也是P450 2D6。由于需要进行特定的治疗干预，自身免疫性肝炎和病毒性肝炎中的自身免疫现象在临床上必须加以区分。这些肝脏疾病可作为研究人类病毒诱导的自身免疫和自身免疫性疾病的模型。
