论文部分内容阅读
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 investigate whether immune tolerance of familial clustered HBV chronic infection is related to CⅡTA-PⅣ methylation. Methods DNA of peripheral blood mononuclear cells (PBMCs) was collected from patients with chronic hepatitis B virus infection in the immune activation stage and immune-active stage HBV infected with first-degree blood relationship in the family. Methylated And unmethylated primers were amplified. Eight clones were randomly selected and sequenced. The sequencing results were submitted to a public database. Results A total of 47 immunocompromised HBV infected persons and 23 immunocompromised patients were collected from 20 pedigrees. The rate of homozygous methylation in the tolerated group was significantly higher than that in the activated group (16/47) 34.0% vs (2/23) 8.7%, χ ~ 2 = 5.194, P = 0.019). The rate of homozygous unmethylation in the tolerated group was significantly lower than that in the activated group (9/47 vs 19.1% vs 10/23) χ ~ 2 = 4.622, P = 0.033). There was no significant difference in heterozygous methylation rates between the two groups. Conclusion Methylation of CⅡTA-PⅣ is associated with immune tolerance in chronic HBV infection. HBV may induce immune tolerance through methylation of CⅡTA-PⅣ and down-regulation of CⅡTA and MHC-Ⅱ antigens.