Computational Regulatory Genomics

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

Helen Brough,  David Cousins,  Alina-Cristina Munteanu,  Yuen Wong,  Asha Sudra,  Kerry Makinson,  Alick Stephens,  Matthew Arno,  Liviu Ciortuz,  Gideon Lack,  Victor Turcanu 
Journal of Allergy and Clinical Immunology 2014 DOI   PubMed  

Abstract

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. 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...
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