Abstract
The causes of severe childhood asthma are poorly understood. Our aim was in this study to define global patterns of gene expression in children with severe therapy-resistant and controlled asthma.
White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip in children with severe, therapy-resistant asthma (SA, n=20), controlled asthma (CA, n=20) and healthy controls (Ctrl, n=19). Receptor expression was studied in separated fractions of leukocytes in adults asthmatics (n=12).
1378 genes were differentially expressed in one or several of the SA vs. Ctrl, SA vs. CA or CA vs. Ctrl contrasts. Three significantly enriched KEGG pathways were represented; natural killer cell mediated cytotoxicity (upregulated in CA), N-Glycan biosynthesis (downregulated in SA) and bitter taste transduction, TAS2Rs (upregulated mostly in SA). qPCR experiments confirmed upregulation of TAS2Rs in the SA group compared to the Ctrl group. Further analysis of sorted leukocyte fractions from adult asthmatics indicated that TAS2R expression was highest in blood lymphocytes. Significant correlations between expression of the TAS2Rs and clinical markers of asthma severity were found in both adults and children.
In conclusion, specific gene expression patterns were observed in children with severe, therapy-resistant asthma. The increased expression of bronchodilatory bitter taste receptors suggests a new target for treatment of asthma.
- ERS