Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes

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• 作者：Sarah J. White^a ; ^c ; Iana H. Haralambieva^a ; ^c ; Inna G. Ovsyannikova^a ; ^c ; Robert A. Vierkant^b ; Megan M. O&rsquo ; Byrne^b ; Gregory A. Poland^a ; ^c ; ^{Poland.Gregory@mayo.edu}
• 关键词：CMI ; cell-mediated immunity ; MMR ; measles/mumps/rubella ; Ab ; antibody ; CDC ; centers for disease control and prevention ; Th1 ; helper T cells
• 出版年：2012
• 期刊代码：75_01988859
• 类别：bio
• 出版时间：June, 2012
• 卷：73
• 期：6
• 页码：636-640
• 文件大小：341 K

摘要

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 鈥渆xtreme鈥?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-纬 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^highCMI^high vs. Ab^lowCMI^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.