Comprehensive analysis of class I and class IIHLA antigens and chronic hepatitis B virus infection
Comprehensive analysis of class I and class IIHLA antigens and chronic hepatitis B virus infection
复制标题
DOI：
10.1128/jvi.77.22.12083-12087.2003
复制
发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Carrington, M
中科院分区：
文献类型：
--
作者：
Thio, CL;Thomas, DL;Carrington, M
急性B型肝炎病毒（HBV）感染后，清除或持续部分取决于宿主免疫应答的活力和广度。由于人类白细胞抗原系统（HLA）是免疫应答的组成部分，我们假设高度多态性的HLA基因是病毒清除的关键决定因素。对194名病毒持续存在的高加索人和342名已清除病毒的匹配对照者进行了HLA I类和II类基因的分子分型。单个I类等位基因A*0301（比值比[OR]，0.47; 95%置信区间[CI]，0.30 - 0.72; P = 0.0005）与病毒清除相关。II类等位基因DRB 1 *1302也与清除率相关（OR，0.42; 95%CI，0.19至0.93; P = 0.03），但在包括与疾病结局相关的其他等位基因作为协变量的多变量模型中，其显著性降低。B*08与病毒持久性相关，既独立相关（OR，1.59; 95%CI，1.04 - 2.43; P = 0.03），也是保守的高加索人单倍型A*01-B*08-DPB 1 *03的一部分。B*44-Cw*1601（OR，2.23; 95% CI，1.13至4.42; P = 0.02）和B*44-Cw*0501（OR，1.99; 95% CI，1.22至3.24; P = 0.006）单倍型也与病毒持续存在相关。有趣的是，B*08单倍型和与B*44-Cw*1601形成单倍型的DR 7均与对HBV疫苗的无应答相关。与I类等位基因的相关性与先前认为的CD 8介导的溶细胞性T细胞应答在决定急性HBV感染结局中的作用一致。
Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DPB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% Cl, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.