CⅡTA-PⅣ甲基化参与家族聚集性HBV感染免疫耐受  

Class Ⅱ transactivator promoter Ⅳ involved in immune-tolerant phase of HBV persistent infection

作　　者：寇小妮[1] 高珩 解新科[1] 郝明霞[1] 刘寰[3] 陈天艳[3] 赵英仁[3] 何英利[3] 王治伦[4] 

机构地区：[1]陕西中医药大学附属医院肝病科,陕西咸阳712000 [2]西安市卫生学校 [3]西安交通大学第一医院肝病研究所 [4]西安交通大学医学院地方病研究所

出　　处：《中国地方病防治》2017年第2期121-124,共4页Chinese Journal of Control of Endemic Diseases

基　　金：国家自然科学基金资助项目(No.81570528);国家"十二五"传染病重大专项(2012ZX10002007)

摘　　要：目的探讨家族聚集性HBV慢性化感染免疫耐受是否与CⅡTA-PⅣ甲基化有关。方法收集家族中具有一级血缘关系的免疫激活期HBV慢性感染者和免疫耐受期HBV慢性感染者,提取外周血单个核细胞的DNA,经亚硫酸氢盐处理后,分别用甲基化的和非甲基化的引物扩增,随机选择8份产物克隆测序,测序结果提交公共数据库。结果共收集来源于20个家系的47个免疫耐受期HBV感染者和23个免疫激活期感染者;耐受组纯合甲基化率显著高于激活组((16/47)34.0%vs(2/23)8.7%,χ~2=5.194,P=0.019);耐受组纯合非甲基化率显著低于激活组((9/47)19.1%VS(10/23)43.5,χ~2=4.622,P=0.033),杂和甲基化率在两组没有统计学差异。结论 CⅡTA-PⅣ甲基化与HBV慢性化感染免疫耐受有关,HBV可能通过甲基化CⅡTA-PⅣ并下调CⅡTA和MHC-Ⅱ类抗原表达而诱导免疫耐受。Objective To examine the relationship between immune tolerance of HBV persistent infection and methylation status of class Ⅱ transactivator promoter Ⅳ（ CⅡTA-P Ⅳ）. Method Patients from clustering-infected families in immune-tolerant phase and in immune-active phase of HBV persistent infection were collected. Blood of each patient was drawn after a written informed-consent was obtained to extract and purify DNA as template for methylation-specific PCR amplification. Randomly selected PCR products were cloned into pMD 18-T vector and then sequenced. Submission of sequencing results to NCBI public data bank was conducted.Result 23 patients in immune-active phase and 47 patients in immune-tolerant phase were collected from20 clustering-infected families. The frequency of homogeneous methylation in immune-tolerant group（ 34.0%,16/47） was significantly higher than that of immune-active group（ 8.7%,2/23）; The frequency of homogeneous unmethylation in immune-tolerant group（ 19.1%,9/47） was significantly lower than that of immune-active group（ 43.5%,10/23）. No statistic significance was found when compared the frequency of heterogeneous methylation in immune-tolerant group with that of immune-active group.Conclusion Immune tolerance of HBV persistent infection associated with methylation of CⅡTA-PⅣ, which probably due to that to escape host immune defense and establish immune tolerance infection of cells with HBV down regulate expression of CⅡTA and MHC-Ⅱinvolving in the prossess of increasing DNA methyltransferase expression and consequently methylation of CⅡTA-PⅣ.

关 键 词：甲基化 免疫耐受 乙型肝炎病毒 MHC-Ⅱ CⅡTA基因 

分 类 号：R373.21[医药卫生—病原生物学]