Genome-wide genetic associations with IFNγ response to smallpox vaccine.
Genome-wide genetic associations with IFNγ response to smallpox vaccine.
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DOI：
10.1007/s00439-012-1179-x
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发表时间：
2012-09
期刊：
影响因子：
5.3
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Kennedy RB;Ovsyannikova IG;Pankratz VS;Haralambieva IH;Vierkant RA;Jacobson RM;Poland GA
天花是一种致命且使人衰弱的疾病，仅在上个世纪就导致数亿人死亡。牛痘病毒为基础的天花疫苗的使用导致了天花的根除。这些疫苗非常有效，在> 97%的接受者中在疫苗部位诱导特征性脓疱或“take”，并诱导广谱的持久体液和细胞免疫应答。个体间疫苗应答变异性背后的机制可能涉及宿主遗传变异，但尚未完全表征。我们在这里报告了第一个天花疫苗反应全基因组关联研究，研究对象是1,000多名最近接受Dryvax®的人。本文提供的数据集中于通过分泌的IFNγ的产生和通过ELISPOT测定法定量IFNγ分泌细胞来测量的细胞免疫应答。我们在基因（RASA 1、ADRA 1D、TCF 7 L1、FAS）中发现了多个显著的SNP相关性，这些基因是直接控制淋巴细胞IFNγ产生或细胞毒性T细胞功能的信号通路的关键组分。同样，我们发现了许多与位于神经细胞功能不可或缺的基因中的SNP相关的研究结果;考虑到神经系统和免疫系统之间复杂的相互作用，这些发现值得在后续研究中进行更深入的研究。
Smallpox is a deadly and debilitating disease that killed hundreds of millions of people in the past century alone. The use of vaccinia-virus based smallpox vaccines led to the eradication of smallpox. These vaccines are remarkably effective, inducing the characteristic pustule or “take” at the vaccine site in > 97% of recipients, and inducing a wide spectrum of long-lasting humoral and cellular immune responses. The mechanisms behind inter-individual vaccine response variability are likely to involve host genetic variation, but have not been fully characterized. We report here the first smallpox vaccine-response genome-wide association study of over 1,000 recent recipients of Dryvax®. The data presented here focus on cellular immune responses as measured by both production of secreted IFNγ and quantitation of IFNγ secreting cells by ELISPOT assay. We identified multiple significant SNP associations in genes (RASA1, ADRA1D, TCF7L1, FAS) that are critical components of signaling pathways that directly control lymphocyte IFNγ production or cytotoxic T cell function. Similarly, we found many associations with SNPs located in genes integral to nerve cell function; findings that, given the complex interplay between the nervous and immune systems, deserve closer examination in follow-up studies.
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DOI：
10.1084/jem.20032083
发表时间：
2004-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Combadiere B;Boissonnas A;Carcelain G;Lefranc E;Samri A;Bricaire F;Debre P;Autran B
通讯作者：
Autran B
影响因子：
4.4
作者：
Crotty, S;Felgner, P;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1016/0006-291x(91)91740-4
发表时间：
1991-09-30
影响因子：
3.1
作者：
BRUNO, JF;WHITTAKER, J;BERELOWITZ, M
通讯作者：
BERELOWITZ, M
影响因子：
30.8
作者：
FRIEDMAN, E;GEJMAN, PV;MCCORMICK, F
通讯作者：
MCCORMICK, F
影响因子：
3.5
作者：
Hanai, N;Nagata, K;Inagaki, M
通讯作者：
Inagaki, M