白细胞介素 18 受体 1 和白细胞介素 18 基因的遗传变异与天花疫苗接种后的干扰素 γ ELISPOT 反应：一种意想不到的关系。
Genetic variation in IL18R1 and IL18 genes and Inteferon γ ELISPOT response to smallpox vaccination: an unexpected relationship.
机构信息
Mayo Clinic Vaccine Research Group.
出版信息
J Infect Dis. 2013 Nov 1;208(9):1422-30. doi: 10.1093/infdis/jit341. Epub 2013 Jul 30.
Abstract
BACKGROUND
Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine-induced adaptive immunity.
METHODS
We examined the association of genetic polymorphisms with cellular (interferon [IFN] γ enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals.
RESULTS
The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus-induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251Phe; P = .01) was significantly associated with an allele dose-related increase in IFN-γ production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN-γ ELISPOT responses (global P < .0001).
CONCLUSIONS
Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine-induced adaptive immunity.
摘要
背景
遗传关联研究表明细胞因子蛋白和细胞因子或细胞因子受体基因多态性在天花疫苗诱导的适应性免疫中起作用。
方法
我们检测了 1076 名接种疫苗者的细胞因子（干扰素 [IFN] γ酶联免疫斑点测定 [ELISPOT]）免疫对天花疫苗的遗传多态性与相关性。
结果
大多数显著关联都发生在 IL18R1 和 IL18 基因中的单核苷酸多态性/单倍型之间，我们之前在本研究队列中报告了与牛痘病毒诱导的中和抗体滴度的关联。一个功能性编码的 IL18R1 多态性（rs1035130/Phe251Phe；P =.01）与 IFN-γ产生的等位基因剂量相关增加显著相关，也与牛痘特异性中和抗体滴度相关。在 IL18R1 单倍型和 IFN-γ ELISPOT 反应的变化之间也发现了显著的相关性（整体 P <.0001）。
结论
我们的数据表明，IL18R1 和 IL18 遗传基因座中的变异对广泛的天花疫苗诱导的适应性免疫具有重要意义。
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