High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma

Abstract

Background

The immunological features of eosinophils in early-onset asthma (EOA) differ from those 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 and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was 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.

Conclusion

This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity 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.

Graphical Abstract

Keywords:

• late-onset asthma
• early-onset asthma
• eosinophils
• messenger RNA

Abbreviations

EOA, early-onset asthma; LOA, late-onset asthma; qRT PCR, quantitative real-time polymerase chain reaction; CCR, C-C motif chemokine receptor; IL-5Rα, interleukin-5 receptor α; IL-17RA, interleukin-17 receptor A; IL-4Rα, interleukin-4 receptor α; CRTH2, prostaglandin D2 receptor 2,; FcεRI, Fcε receptor type I; TGF-β1, transforming growth factor beta 1; AHR, aryl hydrocarbon receptor; TLR, toll-like receptor.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available in the Google drive repository.

[https://drive.google.com/drive/folders/13DXdwj91b2qG4WL9LLTezFFYSNxdsj7a?usp=sharing].

Ethics Approval and Informed Consent

All patients provided written informed consent.

This study was approved by the Chang Gung Medical Foundation Institutional Review Board (No. 201900943A3).

All methods were carried out in accordance with relevant guidelines and regulations complied with the Helsinki declaration.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study is supported by Chang-Gung Memorial Hospital (Grant no. CMRPG3J1361, CMRPG3J1362).