Human Leukocyte Antigen Genotypes in the Genetic Control of Adaptive Immune Responses to Smallpox Vaccine
Human Leukocyte Antigen Genotypes in the Genetic Control of Adaptive Immune Responses to Smallpox Vaccine
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DOI：
10.1093/infdis/jir167
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发表时间：
2011-06-01
影响因子：
6.4
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
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作者：
Ovsyannikova, Inna G.;Vierkant, Robert A.;Poland, Gregory A.
背景人类白细胞抗原（HLA）基因在介导对天花疫苗的适应性免疫应答中的作用尚不清楚。我们确定了一组接受单剂量天花疫苗（Dryvax，Wyeth Laboratories）的个体（n = 1071）的基因型，并在每个位点和每个等位基因水平上检查了HLA等位基因与天花疫苗的15种免疫结果之间的关联。我们发现HLA-B和HLA-DQB 1基因座与牛痘诱导的抗体之间存在显著相关性（每个基因座P = 0.04），HLA-B（星星）1302（P = 0.036）、B（星星）3802（P = 0.011）、DQB 1（星星）0302（P = 0.015）和DQB 1（星星）0604（P = 0.017）等位基因与较高水平相关。在疫苗特异性干扰素（IFN）-γ和DQA 1之间确定了显著的全球相关性（P = .003），白细胞介素（IL）-1 β和HLA-B（P = .004）、肿瘤坏死因子（TNF）-α和HLA-B（P = 0.006），IL-6和HLA-B基因座（P = 0.016）分泌的细胞因子，以及CD 8 α（+）IFN-γ Elispot反应和DQB 1之间（P = 0.027）。携带B（星号）3906（P = .006）和B（星星）5701（P < .001）的受试者比不携带这些等位基因的受试者分泌更高水平的IL-1 β。携带B（星号）5301（P = 0.047）和B（星星）5601（P = 0.008）等位基因的受试者与不携带这些等位基因的受试者相比分泌较少的IL-1 β。B（star）3502（P = .009）、B（star）5601（P = .004）和B（星星）5701（P < .001）等位基因与TNF-α分泌的变化显著相关。这些数据表明，抗体和细胞IFN-γ，IL-1 β，TNF-α和IL-6免疫反应的变化后，接受天花疫苗的遗传控制HLA基因或基因在紧密连锁不平衡这些等位基因。
Background. The role of human leukocyte antigen (HLA) genes in mediating adaptive immune responses to smallpox vaccine remains unknown.Methods. We determined genotypes for a group of individuals (n = 1071) who received a single dose of smallpox vaccine (Dryvax, Wyeth Laboratories) and examined associations between HLA alleles and 15 immune outcomes to smallpox vaccine on a per-locus and a per-allele level.Results. We found significant associations between the HLA-B and HLA - DQB1 loci and vaccinia-induced antibodies (P = .04 for each locus), with the HLA-B(star)1302 (P = .036), B(star)3802 (P = .011), DQB1(star)0302 (P = .015), and DQB1(star)0604 (P = .017) alleles being associated with higher levels. Significant global associations were identified between vaccinia-specific interferon (IFN)-gamma and DQA1 (P = .003), interleukin (IL)-1 beta and HLA-B (P = .004), tumor necrosis factor (TNF)-alpha and HLA-B (P = .006), and IL-6 and HLA-B locus (P = .016) for secreted cytokines, as well as between CD8 alpha(+) IFN-gamma Elispot responses and DQB1 (P = .027). Subjects carrying B(star)3906 (P = .006) and B(star)5701 (P < .001) secreted higher levels of IL-1 beta than did subjects who did not carry these alleles. Subjects carrying the B(star)5301 (P = .047) and B(star)5601 (P = .008) alleles secreted less IL-1 beta, compared with subjects who did not carry these alleles. The B(star)3502 (P = .009), B(star)5601 (P = .004), and B(star)5701 (P < .001) alleles were significantly associated with variations in TNF-alpha secretion.Conclusions. These data suggest that variations in antibody and cellular IFN-gamma, IL-1 beta, TNF-alpha, and IL-6 immune responses after receipt of smallpox vaccine are genetically controlled by HLA genes or genes in close linkage disequilibrium to these alleles.