白细胞介素 9 是儿童花生过敏患者花生特异性记忆 TH 细胞反应的关键组成部分。
IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy.
机构信息
Division of Asthma, Allergy and Lung Biology, King's College London, and Guys' Hospital, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, and Guys' Hospital, London, United Kingdom.
Division of Asthma, Allergy and Lung Biology, King's College London, and Guys' Hospital, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, and Guys' Hospital, London, United Kingdom; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
出版信息
J Allergy Clin Immunol. 2014 Dec;134(6):1329-1338.e10. doi: 10.1016/j.jaci.2014.06.032. Epub 2014 Aug 10.
BACKGROUND
Differentiation between patients with peanut allergy (PA) and those with peanut sensitization (PS) who tolerate peanut but have peanut-specific IgE, positive skin prick test responses, or both represents a significant diagnostic difficulty. Previously, gene expression microarrays were successfully used to identify biomarkers and explore immune responses during PA immunotherapy.
OBJECTIVE
We aimed to characterize peanut-specific responses from patients with PA, subjects with PS, and atopic children without peanut allergy (NA children).
METHODS
A preliminary exploratory microarray investigation of gene expression in peanut-activated memory TH subsets from 3 children with PA and 3 NA children identified potential PA diagnostic biomarkers. Microarray findings were confirmed by using real-time quantitative PCR in 30 subjects (12 children with PA, 12 children with PS, and 6 NA children). Flow cytometry was used to identify the TH subsets involved.
RESULTS
Among 12,257 differentially expressed genes, IL9 showed the greatest difference between children with PA and NA children (45.59-fold change, P < .001), followed by IL5 and then IL13. Notably, IL9 allowed the most accurate classification of children with PA and NA children by using a machine-learning approach with recursive feature elimination and the random forest algorithm. Skin- and gut-homing TH cells from donors with PA expressed similar TH2- and TH9-associated genes. Real-time quantitative PCR confirmed that IL9 was the highest differentially expressed gene between children with PA and NA children (23.3-fold change, P < .01) and children with PS (18.5-fold change, P < .05). Intracellular cytokine staining showed that IL-9 and the TH2-specific cytokine IL-5 are produced by distinct TH populations.
CONCLUSION
In this study IL9 best differentiated between children with PA and children with PS (and atopic NA children). Mutually exclusive production of IL-9 and the TH2-specific cytokine IL-5 suggests that the IL-9-producing cells belong to the recently described TH9 subset.
背景
区分花生过敏（PA）和花生致敏（PS）患者具有挑战性，这些患者可耐受花生，但具有花生特异性 IgE、阳性皮肤点刺试验反应或两者兼有。此前，基因表达微阵列已成功用于鉴定生物标志物并探索 PA 免疫治疗期间的免疫反应。
目的
我们旨在描述 PA 患者、PS 患者和无花生过敏（NA 儿童）的特应性儿童的花生特异性反应。
方法
通过对 3 名 PA 儿童和 3 名 NA 儿童的花生激活记忆 TH 亚群中的基因表达进行初步探索性微阵列研究，鉴定出潜在的 PA 诊断生物标志物。通过实时定量 PCR 在 30 名受试者（12 名 PA 儿童、12 名 PS 儿童和 6 名 NA 儿童）中验证微阵列结果。使用流式细胞术鉴定所涉及的 TH 亚群。
结果
在 12257 个差异表达基因中，IL9 在 PA 儿童和 NA 儿童之间的差异最大（45.59 倍变化，P<0.001），其次是 IL5 和 IL13。值得注意的是，通过使用具有递归特征消除和随机森林算法的机器学习方法，IL9 可以最准确地对 PA 儿童和 NA 儿童进行分类。来自 PA 供体的皮肤和肠道归巢 TH 细胞表达相似的 TH2 和 TH9 相关基因。实时定量 PCR 证实，IL9 是 PA 儿童和 NA 儿童之间差异表达最高的基因（23.3 倍变化，P<0.01）和 PS 儿童（18.5 倍变化，P<0.05）。细胞内细胞因子染色显示，IL-9 和 TH2 特异性细胞因子 IL-5 由不同的 TH 群体产生。
结论
在这项研究中，IL9 可最好地区分 PA 儿童和 PS 儿童（和特应性 NA 儿童）。IL-9 和 TH2 特异性细胞因子 IL-5 的相互排斥产生表明，产生 IL-9 的细胞属于最近描述的 TH9 亚群。
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