Distinct epithelial gene expression phenotypes in childhood respiratory allergy
Distinct epithelial gene expression phenotypes in childhood respiratory allergy
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DOI：
10.1183/09031936.00070511
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发表时间：
2012-05-01
影响因子：
24.3
通讯作者：
Barbry, Pascal
中科院分区：
文献类型：
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作者：
Giovannini-Chami, Lisa;Marcet, Brice;Barbry, Pascal
上皮细胞对儿童过敏性呼吸道疾病的自然史的贡献仍然知之甚少。我们的目的是确定在不同表型的呼吸道过敏中失调的上皮通路。我们建立了尘螨过敏性鼻炎患儿鼻刷的基因表达特征，与控制或不控制哮喘相关或不相关。使用监督学习和无监督聚类来预测患者的不同亚组并定义改变的信号通路。这些特征与用白细胞介素(IL)-4、IL-13、干扰素(IFN)- α t、IFN- β或IFN- γ刺激或体外分化的人鼻上皮细胞原代培养物的特征进行了比较。一种基于61个转录本（包括21个t辅助细胞（Th） 2型应答基因）的监督方法将变应性鼻炎儿童与健康对照区分（预测准确率为91%）。然后将该方法应用于预测控制或不控制哮喘的儿童（预测准确率为75%），基于41个转录本：其中9个转录本在不控制哮喘中下调，与IFN直接相关。该组还包括与哮喘遗传相关的GSDML。我们的数据显示th2驱动的上皮表型在所有患有尘螨过敏性鼻炎的儿童中都是常见的。它强调了上皮表达分子对哮喘控制的影响，与特应性和受损的病毒反应有关。
Epithelial cell contribution to the natural history of childhood allergic respiratory disease remains poorly understood. Our aims were to identify epithelial pathways that are dysregulated in different phenotypes of respiratory allergy.We established gene expression signatures of nasal brushings from children with dust mite-allergic rhinitis, associated or not associated with controlled or uncontrolled asthma. Supervised learning and unsupervised clustering were used to predict the different subgroups of patients and define altered signalling pathways. These profiles were compared with those of primary cultures of human nasal epithelial cells stimulated with either interleukin (IL)-4, IL-13, interferon (IFN)-alpha t, IFN-beta or IFN-gamma, or during in vitro differentiation.A supervised method discriminated children with allergic rhinitis from healthy controls (prediction accuracy 91%), based on 61 transcripts, including 21 T-helper cell (Th) type 2-responsive genes. This method was then applied to predict children with controlled or uncontrolled asthma (prediction accuracy 75%), based on 41 transcripts: nine of them, which were down-regulated in uncontrolled asthma, are directly linked to IFN. This group also included GSDML, which is genetically associated with asthma.Our data revealed a Th2-driven epithelial phenotype common to all children with dust mite allergic rhinitis. It highlights the influence of epithelially expressed molecules on the control of asthma, in association with atopy and impaired viral response.