Ovsyannikova Inna G, Vierkant Robert A, Pankratz V Shane, O'Byrne Megan M, Jacobson Robert M, Poland Gregory A
Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
Vaccine. 2009 May 26;27(25-26):3349-58. doi: 10.1016/j.vaccine.2009.01.080. Epub 2009 Feb 5.
Secreted rubella virus-specific cytokines reflect the immunologic mechanisms underlying adoptive immune responses and are significant markers of immunity to rubella. We studied the association between measures of cellular (cytokine and frequency of cytokine-secreted cells) immune responses and HLA haplotypes (with frequencies of > or =1%) and supertypes among 738 healthy children following two doses of rubella vaccine. Haplotype effects were estimated while accounting for linkage phase ambiguity via an expectation maximization algorithm. Importantly, the majority of HLA class I and class II haplotype associations with different cytokines were consistent between Th1, Th2 and/or innate/proinflammatory cytokine groups. We found few class I supertypes (A1, A2, A3, and B7) with potential associations with IL-10 ELISPOT counts and rubella-specific IL-2, IL-10, TNF-alpha, and IL-6 cytokine secretion levels. Our data indicate that the presence or absence of certain HLA haplotypes and/or supertypes may influence the cytokine immune response to rubella vaccine, and represents a more advanced analysis compared to individual candidate gene association studies.
分泌的风疹病毒特异性细胞因子反映了过继性免疫反应的免疫机制，是风疹免疫的重要标志物。我们研究了738名健康儿童接种两剂风疹疫苗后细胞免疫反应指标（细胞因子和细胞因子分泌细胞频率）与HLA单倍型（频率≥1%）及超级型之间的关联。通过期望最大化算法估计单倍型效应，同时考虑连锁相模糊性。重要的是，大多数HLAⅠ类和Ⅱ类单倍型与不同细胞因子的关联在Th1、Th2和/或固有/促炎细胞因子组之间是一致的。我们发现少数Ⅰ类超级型（A1、A2、A3和B7）与IL-10 ELISPOT计数以及风疹特异性IL-2、IL-10、TNF-α和IL-6细胞因子分泌水平可能存在关联。我们的数据表明，某些HLA单倍型和/或超级型的存在与否可能影响对风疹疫苗的细胞因子免疫反应，与单个候选基因关联研究相比，这是一种更深入的分析。
