乙型重型肝炎基因变异与免疫异常的关系

The relationship between the HBV gene mutation and the abnormal immunity of host

目的 探讨在重型肝炎中 ,乙型肝炎病毒 (HBV)前C区 1896位基因突变与机体免疫水平的关系。方法 采用限制性酶切片段长度多态性分析 (RFLP)检测HBV基因组前C区 1896位是否存在变异 ,以单克隆抗体APAAP法比较末梢血T细胞亚群的分布情况 ,用双抗体夹心ELISA法检测血清细胞因子 (TNF α、IFN γ、IL 6、IL 8)水平。结果 2 3例重型肝炎中 ,HBV基因变异株感染率为 5 2 .2 % ,而 2 2例急性乙型肝炎中仅 1例为变异株感染 ;变异株组CD8+ T细胞百分率明显下降 ,CD4+ /CD8+ 比值明显增高 ,CD3+ 、CD4+ T细胞的百分率未见明显变化 ;重型肝炎中细胞因子(TNF α、IFN γ、IL 6、IL 8)水平均明显高于急性乙型肝炎相应之细胞因子水平 ,而变异株组IFN γ、IL 6水平明显高于非变异株组 ,TNF α和IL 8在两组间无明显差异 ;变异株组病死率 (10 0 % )明显高于野毒株组的病死率 (9% )。结论 重型肝炎中 ,变异株HBV感染率很高 ;基因变异的HBV可能通过各种途径刺激机体的免疫系统 ,使免疫细胞活化 ,从而释放大量细胞因子 ,导致肝细胞损伤 。

Objective To study the relationship between the HBV precore 1896 site mutation and the host immunity. Methods HBV precore 1896 site mutation was confirmed by restriction fragment length polymorphism analysis; The cytokines(TNF α、IFN γ、IL 6 and IL 8) levels were measured by enzyme linked immunosorbent assay(ELISA) and T subpopulations by APAAP. Results In fulminant hepatitis, the infective rate of HBV mutate type was 52.5%, while only one patient was infected by mutate type virus in acute hepatitis; The percentage of CD8 +T lymphocyte was obviously lower and the ratio of CD4 +/CD8 + was obviously higher in mutate group than wild strain group; The cytokine levels in the patients with fulminant hepatitis were higher than those in acute hepatitis. The mortality of patients with mutate type was higher(100%) than that of wild type(9%). Conclusion In fulminant hepatitis, the infective rate of HBV mutate type is high. The mutate type virus provokes host immune system resulting in the activation of lymphocyte and release of cytokines, which contributed to severe liver damage.