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

2014; Elsevier BV; Volume: 134; Issue: 6 Linguagem: Inglês

10.1016/j.jaci.2014.06.032

1097-6825

Helen A. Brough, David J. Cousins, Alina Munteanu, Yuen Fei Wong, Asha Sudra, Kerry Makinson, Alick Stephens, Matthew Arno, Liviu Ciortuz, Gideon Lack, Victor Turcanu,

Allergic Rhinitis and Sensitization

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.We aimed to characterize peanut-specific responses from patients with PA, subjects with PS, and atopic children without peanut allergy (NA children).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.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.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.