基因芯片筛查哮喘患者外周血CD4+T细胞差异表达基因

Transcriptomic microarray profiling of peripheral CD4+ T-cells from asthmatic patients

目的应用基因芯片技术检测轻中度持续哮喘患者与正常人CD4+T淋巴细胞之间差异表达基因,探索哮喘可能相关的生物信号通路,阐明CD4+T淋巴细胞在哮喘发生发展中作用。方法应用芯片检测CD4+T细胞全基因组表达谱;Ingenuity通路分析软件(IPA)对差异表达基因进行注释并进行富集分析。结果与正常对照比较,哮喘患者CD4+T淋巴细胞中997个基因表达显著异常,其中上调805个、下调192个,有38个注释基因的相对表达量变化达4倍及以上;相关性分析表明CD300A与嗜酸粒细胞绝对值(r=-0.89,P=0.02)和百分比(rs=-0.94,P=0.004)成反比,CSF1R与PD20(rs=-0.83,P=0.04)和AQLQ(r=-0.88,P=-0.02)成反比。结论哮喘的发生涉及众多生物信号通路的异常调节,对进一步探索哮喘的发病机制提供了理论依据。

Objective To identify differentially expressed genes in peripheral blood mononuclear cells between patients with continuous mild-to-moderate asthma and healthy controls using mRNA microarray in order to explore the underlying signaling pathways and clarify the roles of CD4+T cells in the pathogenesis of asthma.Methods Global transcriptomic profiles of the CD4+T cells were defined by using Agilent Sure Print G3 Human GE 8×60K microarray.Enrichment pathways were analyzed with Ingenuity Pathway Analysis (IPA)software.Results Compared with controls,805genes were up-regulated,192 were down-regulated in asthma patients.Among these,the expression of 38 annotated genes have varied by 4 times or more.Expression of CD3OOA was inversely proportional to the absolute value of eosinophils (r=-0.89, P=0.02)as well as the proportion of eosinophils (rs=-0.94,P=0.004),while CSF1R was inversely proportional to PD20(rs=-0.83,P=0.04)and AQLQ (r=-0.88,P=0.02)by correlation analysis. Conclusion Numerous pathophysiologicaI pathways may be involved in the pathogenesis of asthma.Above findings have provided a basis for the delineation the pathogenesis of asthma.