High transcriptional activity and clinical correlations in eosinophils of patients with late-onset asthma

Abstract

Abstract Background The immunological features of eosinophils in early-onset asthma (EOA) differs from that in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods Eosinophils obtained from well controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes (integrins α4 and β2, CCR3, CCR5, and IL-5Rα, and IL-17RA) and specific markers (IL-4Rα, prostaglandin D2 receptor 2, high-affinity IgE receptor, TGF-β1, aryl hydrocarbon receptor, and endosomal TLR-3, 7, and 9) in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function were further analyzed. Results The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. There was no significant correlation between mRNA expression and treatment control levels among LOA or EOA patients Conclusion This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obese by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.