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Boeck, A.* ; Landgraf-Rauf, K.* ; Vogelsang, V.* ; Siemens, D.* ; Prazeres da Costa, O.* ; Klucker, E.* ; von Mutius, E. ; Buch, T.* ; Mansmann, U.* ; Schaub, B.*

Ca2+ and innate immune pathways are activated and differentially expressed in childhood asthma phenotypes.

Pediatr. Allergy Immunol. 29, 823-833 (2018)
Postprint DOI PMC
Open Access Green
Background Asthma is the most common chronic disease in children. Underlying immunologic mechanisms-in particular of different phenotypes-are still just partly understood. The objective of the study was the identification of distinct cellular pathways in allergic asthmatics (AA) and nonallergic asthmatics (NA) vs healthy controls (HC). Methods Peripheral blood mononuclear cells (PBMCs) of steroid-naive children (n(AA/NA/HC) = 35/13/34)) from the CLARA study (n = 275) were stimulated (anti-CD3/CD28, LpA) or kept unstimulated. Gene expression was investigated by transcriptomics and quantitative RT-PCR. Differentially regulated pathways between phenotypes were assessed after adjustment for sex and age (KEGG pathways). Networks based on correlations of gene expression were built using force-directed graph drawing. Results Allergic asthmatics vs NA and asthmatics overall vs HC showed significantly different expression of Ca2+ and innate immunity-associated pathways. PCR analysis confirmed significantly increased Ca2+-associated gene regulation (ORMDL3 and ATP2A3) in asthmatics vs HC, most prominent in AA. Innate immunity receptors (LY75, TLR7), relevant for virus infection, were also upregulated in AA and NA compared to HC. AA and NA could be differentiated by increased ATP2A3 and FPR2 in AA, decreased CLEC4E in AA, and increased IFIH1 expression in NA following anti-CD3/28 stimulation vs unstimulated (fold change). Conclusions Ca2+ regulation and innate immunity response pattern to viruses were activated in PBMCs of asthmatics. Asthma phenotypes were differentially characterized by distinct regulation of ATP2A3 and expression of innate immune receptors (FPR2, CLEC4E, IFIH1). These genes may present promising targets for future in-depth investigation with the long-term goal of more phenotype-specific therapeutic interventions in asthmatics.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Ormdl3; Identification; Cells; Risk
ISSN (print) / ISBN 0905-6157
e-ISSN 1399-3038
Zeitschrift Pediatric Allergy and Immunology
Quellenangaben Band: 29, Heft: 8, Seiten: 823-833 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Asthma and Allergy Prevention (IAP)