Mayo Clinic Vaccine Research Group, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Hum Immunol. 2012 Jun;73(6):636-40. doi: 10.1016/j.humimm.2012.03.015. Epub 2012 Apr 12.
Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four "extreme" humoral (Ab(high/low)) and CMI (CMI(high/low)) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for Ab(high)CMI(high) vs. Ab(low)CMI(low)). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.
我们的目的是复制先前报道的细胞因子和细胞因子受体 SNP 与麻疹疫苗体液和细胞介导免疫（CMI）反应之间的关联。所有受试者（n=758）均接受了两剂 MMR（麻疹/腮腺炎/风疹）疫苗。从这些受试者中，选择了候选细胞因子和细胞因子受体 SNP 进行基因分型，并在 29-30 名受试者中进行了分析，这些受试者分为四个“极端”体液（Ab（高/低）和 CMI（高/低）反应象限之一。使用卡方检验评估了 11 个 SNP 中的 7 个（在发现研究中）与麻疹特异性中和抗体水平和 IFN-γ ELISPOT 反应之间的关联。我们在 IL12RB1 基因中的 SNP rs372889 发现了一个复制的关联（Ab（高）CMI（高）与 Ab（低）CMI（低）相比，P=0.03）。我们的研究结果表明，使用免疫表型极端值和较小的样本量复制基因型表型关联非常重要。我们推测，IL12RB1 多态性可能影响 IL-12 和 IL-23 的结合及其下游效应，这是麻疹疫苗 CMI 反应中的关键细胞因子。
