The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex.

The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex.
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DOI:
10.1186/1471-2466-11-17
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发表时间:
2011-04-07
影响因子:
3.1
通讯作者:
Raby BA
Raby BA
中科院分区:
医学3区
文献类型:
--
作者:
Hunninghake GM;Chu JH;Sharma SS;Cho MH;Himes BE;Rogers AJ;Murphy A;Carey VJ;Raby BA

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血清总IgE水平与外周血CD4+T细胞基因表达模式之间的关系尚不清楚(在所有受试者中,特别是在性别之间)。来自儿童哮喘管理计划(CAMP)的223名参与者的外周血中的CD4+T细胞,同时测定IgE。提取总RNA,并用Illumina Human Ref8 v2珠芯片阵列产生表达谱。对所有受试者的全基因组基因转录水平和IgE水平之间的关系进行建模,并按性别分层。在所有受试者中,单基因白介素17受体B(IL17RB)的基因转录丰度与IgE之间存在显著的相关性,解释了IgE测定中12%的变异(R2=7×10-7,经多次检测调整后的p值为9×10-3)。性别分层分析显示,IL17RB与IgE的相关性仅限于男性(R2=0.19,p值=8×10-8;性别交互作用检验p<0.05)。在女性中,基因转录丰度与IgE水平之间未发现显著相关性。此外,在考虑多基因模型时,以及在对IgE水平的典型路径分析中,我们还显示了显著的性别差异。我们的结果表明,IL17RB可能是唯一一个在CD4+T细胞中表达的基因,其转录水平与哮喘患者IgE水平的变化相关。这些结果提供了进一步的证据,性别可能在IgE的基因组调控中发挥作用。
The relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex specifically) are not known. Peripheral blood CD4+ T cells from 223 participants from the Childhood Asthma Management Program (CAMP) with simultaneous measurement of IgE. Total RNA was isolated, and expression profiles were generated with Illumina HumanRef8 v2 BeadChip arrays. Modeling of the relationship between genome-wide gene transcript levels and IgE levels was performed in all subjects, and stratified by sex. Among all subjects, significant evidence for association between gene transcript abundance and IgE was identified for a single gene, the interleukin 17 receptor B (IL17RB), explaining 12% of the variance (r2) in IgE measurement (p value = 7 × 10-7, 9 × 10-3 after adjustment for multiple testing). Sex stratified analyses revealed that the correlation between IL17RB and IgE was restricted to males only (r2 = 0.19, p value = 8 × 10-8; test for sex-interaction p < 0.05). Significant correlation between gene transcript abundance and IgE level was not found in females. Additionally we demonstrated substantial sex-specific differences in IgE when considering multi-gene models, and in canonical pathway analyses of IgE level. Our results indicate that IL17RB may be the only gene expressed in CD4+ T cells whose transcript measurement is correlated with the variation in IgE level in asthmatics. These results provide further evidence sex may play a role in the genomic regulation of IgE.
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