Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Infect Dis. 2011 Jun 1;203(11):1546-55. doi: 10.1093/infdis/jir167.
The role of human leukocyte antigen (HLA) genes in mediating adaptive immune responses to smallpox vaccine remains unknown.
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.
We found significant associations between the HLA-B and HLA - DQB1 loci and vaccinia-induced antibodies (P = .04 for each locus), with the HLA-B1302 (P = .036), B3802 (P = .011), DQB10302 (P = .015), and DQB10604 (P = .017) alleles being associated with higher levels. Significant global associations were identified between vaccinia-specific interferon (IFN)-γ and DQA1 (P = .003), interleukin (IL)-1β and HLA-B (P = .004), tumor necrosis factor (TNF)-α and HLA-B (P = .006), and IL-6 and HLA-B locus (P = .016) for secreted cytokines, as well as between CD8α(+) IFN-γ Elispot responses and DQB1 (P = .027). Subjects carrying B3906 (P = .006) and B5701 (P < .001) secreted higher levels of IL-1β than did subjects who did not carry these alleles. Subjects carrying the B5301 (P = .047) and B5601 (P = .008) alleles secreted less IL-1β, compared with subjects who did not carry these alleles. The B3502 (P = .009), B5601 (P = .004), and B*5701 (P < .001) alleles were significantly associated with variations in TNF-α secretion.
These data suggest that variations in antibody and cellular IFN-γ, IL-1β, TNF-α, 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.
人类白细胞抗原（HLA）基因在介导对天花疫苗的适应性免疫反应中的作用尚不清楚。
我们确定了一组接受单一剂量天花疫苗（Dryvax，惠氏实验室）的个体（n=1071）的基因型，并在每个基因座和每个等位基因水平上检查了 HLA 等位基因与 15 种天花疫苗免疫反应之间的关联。
我们发现 HLA-B 和 HLA-DQB1 基因座与痘苗诱导的抗体之间存在显著关联（每个基因座 P=0.04），HLA-B1302（P=0.036）、B3802（P=0.011）、DQB10302（P=0.015）和 DQB10604（P=0.017）等位基因与较高水平相关。在痘苗特异性干扰素（IFN）-γ和 DQA1（P=0.003）、白细胞介素（IL）-1β和 HLA-B（P=0.004）、肿瘤坏死因子（TNF）-α和 HLA-B（P=0.006）以及 IL-6 和 HLA-B 基因座（P=0.016）之间，我们鉴定到了与分泌细胞因子相关的显著的总体关联，以及 CD8α（+）IFN-γ Elispot 反应与 DQB1（P=0.027）之间的关联。与不携带这些等位基因的个体相比，携带 B3906（P=0.006）和 B5701（P<0.001）等位基因的个体分泌更高水平的 IL-1β。与不携带这些等位基因的个体相比，携带 B5301（P=0.047）和 B5601（P=0.008）等位基因的个体分泌的 IL-1β 较少。B3502（P=0.009）、B5601（P=0.004）和 B*5701（P<0.001）等位基因与 TNF-α 分泌的变化显著相关。
这些数据表明，天花疫苗接种后抗体和细胞 IFN-γ、IL-1β、TNF-α 和 IL-6 免疫反应的变化受 HLA 基因或与这些等位基因紧密连锁的基因控制。
