乙型肝炎患者HBV X蛋白特异性CTL表位变异分析  

Mutation analysis of cytotoxic T lymphocyte epitopes derived from HBV X protein in patients with hepatitis B

作　　者：刘志国[1] 许智慧[2] 洪炜[1] 刘佳[1] 任晓强[2] 刘妍[2] 毛远丽[1] 徐东平[2] 

机构地区：[1]解放军三○二医院临床检验中心,北京100039 [2]解放军三○二医院传染病研究所病毒性肝炎研究室,北京100039

出　　处：《胃肠病学和肝病学杂志》2010年第1期67-70,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家重点基础研究发展计划(973计划)课题资助项目(2007CB512803);国家自然科学基金资助项目(30771898)

摘　　要：目的比较急性乙型肝炎、慢性乙型肝炎与慢性重型乙型肝炎HBVX蛋白特异性CTL表位变异差异,探讨乙型肝炎重症化和慢性化的可能机理。方法对393例乙型肝炎患者的血清样本进行HLA-A2分型;用巢式PCR扩增血清HBV前S/S基因与X基因并对PCR产物进行序列测定;根据HBV前S/S基因序列,用VirusBlast软件鉴定患者感染的HBV基因型;用Vector NTI软件对目前已知的6个HLA-A2限制性X蛋白特异性CTL表位序列分析,对患者各个表位变异的差异进行卡方检验。结果190例(48.35%)患者HLA-A2阳性,其中急性乙型肝炎(AHB)67例,慢性乙型肝炎(CHB)52例,慢性重型乙型肝炎(CSHB)71例。CTL表位变异分析结果如下:对三组所有患者进行比较时,X92-100表位变异发生频数三组患者比较有非常显著性差异(P<0.01);对三组中HBV C基因型患者进行比较时,X92-100和X115-123表位变异发生频数三组患者比较有显著性差异(P<0.05);对三组中HBV B基因型患者进行比较时,各表位变异发生频数三组患者比较无显著差异。结论某些HBVX蛋白特异性CTL表位在AHB、CHB和CSHB患者间变异有明显差异且受病毒基因型影响,CTL表位变异可能与乙型肝炎的重症化和慢性化机制相关。Objective To explore the possible mechanisms of severity and chronicity of hepatitis B by comparing mutation occurrence of HBV X protein-specific CTL epitopes among patients with acute hepatitis B（AHB）,chronic hepatitis B（CHB） and chronic severe hepatitis B（CSHB）.Methods HLA-A2 typing was performed for 393 patients with hepatitis B.Nested PCR was used to amplify HBV PreS/S gene and X gene followed by sequencing of PCR products.HBV genotyping was determined based on the PreS/S gene sequence by VirusBlast software.The mutations of 6 HLA-A2-restricted X protein-specific CTL epitopes were analyzed by Vector NTI software.The difference was calculated by χ2 test.Results One hundred and ninety（48.35%） patients were identified as HLA-A2 positive.Thereinto,67 patients were AHB,52 CHB and 71 CSHB.The results of CTL epitope mutation were as follows： when all patients of AHB,CHB and CSHB groups were enrolled,there was significant difference（P0.05） in the mutation occurrence of X92-100 epitopes among the three groups;when only HBV genotype C patients were enrolled,there was significant difference（P0.05） in the mutation occurrence of X92-100 and X115-123 epitopes among the three groups;when only HBV genotype B patients were enrolled,the mutation diversity was not found in the three groups.Conclusion Obvious difference exists in the mutation occurrence of a few HBV X protein epitopes which is affected by HBV genotype.The mutation factor is possibly associated with the pathogenesis of severity and chronicity of hepatitis B.

关 键 词：乙型肝炎病毒 特异性CTL表位 X区蛋白 

分 类 号：R512.62[医药卫生—内科学]