RT Journal Article
SR Electronic
T1 Distinct epithelial gene expression phenotypes in childhood respiratory allergy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1197
OP 1205
DO 10.1183/09031936.00070511
VO 39
IS 5
A1 Lisa Giovannini-Chami
A1 Brice Marcet
A1 Chimène Moreilhon
A1 Benoît Chevalier
A1 Marius I. Illie
A1 Kévin Lebrigand
A1 Karine Robbe-Sermesant
A1 Thierry Bourrier
A1 Jean-François Michiels
A1 Bernard Mari
A1 Dominique Crénesse
A1 Paul Hofman
A1 Jacques de Blic
A1 Laurent Castillo
A1 Marc Albertini
A1 Pascal Barbry
YR 2012
UL http://erj.ersjournals.com/content/39/5/1197.abstract
AB 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.