中文摘要：

目的基于一个完整的乙型肝炎病毒（HBV）感染自然史的4个时期（免疫耐受期、免疫清除期、不活动期和HBeAg阴性肝炎阶段）,研究HBV表面抗原各抗原表位的免疫逃逸突变分布。方法收集280例患者的临床资料及血清标本,按照HBV自然史的不同时期分为4组,提取DNA并荧光定量,通过巢式PCR扩增HBV表面基因序列,以PCR产物作为模板进行DNA测序。分析比较4组乙肝表面抗原中辅助性T细胞（Th）表位、细胞毒性T淋巴细胞（CTL）表位及B细胞抗原表位的突变差异。结果 Th抗原表位突变中,4组间比较具有差异的是17-31、37-51、67-81等区域,CTL抗原表位突变中具有差异的是14-22、41-49等区域,在B细胞抗原表位区域发现了Q101K、P120S、T126S、Q129H、M133L、M133I、和M133T等7个乙肝表面抗原免疫逃逸突变。结论在HBV感染自然史中,表面抗原突变的累积发生在免疫清除期,突变的产生有利于HBV逃避免疫系统的攻击。

英文摘要：

Objective To investigate the distribution of the immune escape mutations of hepatitis B virus surface antigen across the natural history of hepatitis B virus infection.Methods A total of 280 patients were divided into four groups according to the natural history of hepatitis B virus infection.DNA was extracted,and the gene sequences of hepatitis B virus surface autigen were amplified by using nested PCR.The PCR product served as a template for DNA sequencing.The differences of mutations in epitopes of helper T cells（Th）,cytotoxic T lymphocytes（CTL）and B cells were analyzed.Results Among the four groups,there were significant differences in mutations of epitopes of Th at regions of 17-31,37-51,67-81,and in mutations of epitopes of CTL at regions of 14-22 and 41-49 among the four groups.Immune escape mutations of hepatitis B virus surface antigen were found in epitopes of B cells in all four groups,namely Q101K,P120S,T126S,Q129H,M133L,M133I and M133T.Conclusion The mutations within the immune epitopes accumulated in the immune clearance phase across the natural history,indicating their potential role in evading the immune system attacks.