HBV C基因区表位变异与慢加急性肝功能衰竭的相关性  

Epitope mutations in HBV core gene associated with the morbidity of acute-on-chronic liver failure

作　　者：杨玲[1] 曾文铤[1] 谢栩硕[1] 梁增伟[1] 区映研[1] 

机构地区：[1]广州医学院第一附属医院感染科,510120

出　　处：《肝脏》2013年第7期448-451,共4页Chinese Hepatology

基　　金：广东省科技厅课题(粤科社字[2011]106号);广州医学院课题(2011C36);广州医学院第一附属医院课题(y201006-gyfy)

摘　　要：目的通过分析HBVC基因区病毒的变异,探讨HBcAg区表位变异与慢加急性肝衰竭(ACLF)发病的关系。方法收集39例ACLF、38例严重肝炎活动(SHB)和44例慢性乙型肝炎(CHB)患者的血标本,PCR扩增HBVC基因区,分析HBcAg区表位的变异。分离单核淋巴细胞,流式细胞术检测HLA-A2分型。结果与CHB组比较,ACLF组HBVC基因区发生高频率的变异,且变异的位点绝大部分位于表位区域:core27(I-V,26.32%比4.76%,P=0.007)位于HLA-A2限制性表位CTL18-27区,core5、core35和core60分别位于Th细胞表位区,core83位于B细胞表位区。对包含变异体CTL18-27(27V)的ACLF和SHB患者随访3个月以上,5例HLA-A2阳性患者均变异为野生株I27;而5例HLA-A2阴性的患者,随访后包含V27的病毒仍然能被检测出(5/0比0/5,P=0.008)。结论 HBVC基因区高频率的氨基酸变异导致的表位变异,可能通过增强表位的免疫原性参与ACLF的发病。Objective Studies showed that the emergence of mutations within T cell or B cell epitopes of HBV, which produced vigorous host immune response, precipitated severe liver inflammation. In this study, the nucleotide sequences in HBV core gene were analyzed to investigate the relationship between the epitope mutations and HBV-related acute-on-chronic liver failure（ACLF）. Methods Thirty-nine patients with ACLF, 38 with severe hepatitis B （SHB） and 44 with chronic hepatitis B （CriB） were involved in the study. Sequences of HBV core gene were determined by PCR. HLA-A2 typing was analyzed by peripheral blood mononuclear cells stained on a FACS flow cytometer. Results The frequency of amino acid variability including core27, coreS, core60, core83 and core135 in HBV core gene were significantly higher in ACLF patients than that in CHB patients whose sites located within CTL18 27, Th cell epitopes or B cell epitopes, respectively. ACLF and SHB patients with CTL18-27 （27 V ） were followed up for at least 3 months. Among 5 HLA-A2 positive cases, CTL18-27（27V） was not detected and could change into wild-type CTL18-27（27I）. On contrary, CTL18-27（27V） could still be detected among 5 HLA-A2 negative cases （5/0 vs. 0/5, P = 0. 008）. Conelusion The epitope mutations in HBV core gene which up-regulated epitope immunodominance play an important role in the development of ACLF.

关 键 词：乙型肝炎病毒 慢加急性肝衰竭 表位变异 免疫反应 

分 类 号：R575.3[医药卫生—消化系统]