title: Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
abstract: 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)-α, IFN-β or IFN-γ, 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.
authors: CNRS and University of Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Sophia Antipolis, 06560 Sophia Antipolis, France.
authors: Lisa
authors: L
authors: Giovannini-Chami
authors: Brice
authors: B
authors: Marcet
authors: Chimène
authors: C
authors: Moreilhon
authors: Benoît
authors: B
authors: Chevalier
authors: Marius I
authors: MI
authors: Illie
authors: Kévin
authors: K
authors: Lebrigand
authors: Karine
authors: K
authors: Robbe-Sermesant
authors: Thierry
authors: T
authors: Bourrier
authors: Jean-François
authors: JF
authors: Michiels
authors: Bernard
authors: B
authors: Mari
authors: Dominique
authors: D
authors: Crénesse
authors: Paul
authors: P
authors: Hofman
authors: Jacques
authors: J
authors: de Blic
authors: Laurent
authors: L
authors: Castillo
authors: Marc
authors: M
authors: Albertini
authors: Pascal
authors: P
authors: Barbry
mesh_terms: D000293:Adolescent; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines