RT Journal Article
SR Electronic
T1 Allergic and non-allergic childhood asthma is characterized by novel biomarkers and signaling pathways
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4208
VO 44
IS Suppl 58
A1 Diana Raedler
A1 Olivia Prazeres da Costa
A1 Nikolaus Ballenberger
A1 Elisabeth Klucker
A1 Julia Roeb
A1 Erika von Mutius
A1 Thorsten Buch
A1 Ulrich Manmann
A1 Bianca Schaub
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P4208.abstract
AB Background: Different childhood asthma phenotypes have been reported. However their distinct immune pathogenesis is still not well defined.Objective: To identify biomarkers and pathways for the differentiation of allergic (AA) and non-allergic asthmatic (NA) children in comparison to healthy controls (HC).Methods: In the CLARA study population (n=260) peripheral blood mononuclear cells (PBMCs: n(AA/NA/HC)=(14/8/14)) and CD4+ cells of a subset of children, comparable to the whole population, were stimulated with anti-CD3/CD28, LpA or kept unstimulated. Gene-expression was investigated by microarray and qRT-PCR. Microarray data were analyzed with explorative screening methods using empirical Bayes linear modelling and confirmatory procedures applying global tests of differentially expressed cell-type-associated and pathway genes.Results: AA were characterized by differential transcriptional regulation of mTOR-signaling with increased expression of Treg-associated genes and decreased IRF8, involved in intracellular defence against pathogens. NA were characterized by differential regulation of TLR-signaling and increased expression of genes associated with Calcium-signaling (INPP5B), airway remodeling (ETS2, HNMT) or both (S100A8, S100A9). Expression of Th2 genes was increased in AA and NA compared to HC. Microarray analysis of PBMCs identified more differentially regulated pathways than analysis of CD4+ cells.Conclusion: Childhood allergic and non-allergic asthma was differentiated by novel specific gene expression profiles, suggesting unique concepts of immune mechanisms. These open novel perspectives for prognosis, phenotype-specific therapies and treatment response.