IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy

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 suc...

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Veröffentlicht in:Journal of allergy and clinical immunology 2014-12, Vol.134 (6), p.1329-1338.e10
Hauptverfasser: Brough, Helen A., MSc, FRCPCH, Cousins, David J., PhD, Munteanu, Alina, MSc, Wong, Yuen Fei, PhD, Sudra, Asha, MSc, Makinson, Kerry, MSc, Stephens, Alick C., PhD, Arno, Matthew, PhD, Ciortuz, Liviu, PhD, Lack, Gideon, FRCPCH, MD, Turcanu, Victor, MD, PhD
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Sprache:eng
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Zusammenfassung: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 TH 2- and TH 9-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 TH 2-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 TH 2-specific cytokine IL-5 suggests that the IL-9–producing cells belong to the recently described TH 9 subset.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2014.06.032