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[摘要]：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. |
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