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.