AUTHOR=Elena-Pérez Sandra , Heredero-Jung David Hansoe , García-Sánchez Asunción , Estravís Miguel , Martin Maria J. , Ramos-González Jacinto , Triviño Juan Carlos , Isidoro-García María , Sanz Catalina , Dávila Ignacio 

TITLE=Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.624576

DOI=10.3389/fmed.2020.624576

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Asthma is a heterogeneous syndrome with a broad clinical spectrum and high drug response variability. The inflammatory response in asthma involves multiple effector cells and mediator molecules. Based on asthma immunopathogenesis, precision medicine can be a promising strategy for identifying biomarkers. Biologic therapies acting on the IL-5/IL-5 receptor axis have been developed. IL-5 promotes proliferation, differentiation and activation of eosinophils by binding to the IL-5 receptor, located on the surface of eosinophils and basophils. This study aimed to investigate the expression of <italic>IL5RA</italic> in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha.</p><p><bold>Methods:</bold> Sixty peripheral blood samples, 30 from healthy controls and 30 from asthmatic patients, were selected for a transcriptomic RNAseq study. Differential expression analysis was performed by statistical assessment of fold changes and <italic>P</italic>-values. A validation study of <italic>IL5RA</italic> expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on <italic>IL5RA</italic> expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The <italic>IL5RA</italic> mRNA levels were normalized to <italic>GAPDH</italic> and <italic>TBP</italic> expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines.</p><p><bold>Results:</bold><italic>IL5RA</italic> was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients (<italic>P</italic> = 8.63E-08 and fold change of 2.22). In the qPCR validation study, <italic>IL5RA</italic> expression levels were significantly higher in asthmatic patients than in controls (<italic>P</italic> &lt; 0.001). Significant expression differences were present in different asthmatic types. In the biological drug study, patients treated with benralizumab showed a significant decrease in <italic>IL5RA</italic> expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients.</p><p><bold>Conclusions:</bold> These results indicate that <italic>IL5RA</italic> is overexpressed in patients with different types of asthma. It could help identify which asthmatic patients will respond more efficiently to benralizumab, moving toward a more personalized asthma management. Although further studies are required, <italic>IL5RA</italic> could play a role as a biomarker and pharmacogenetic factor in asthma.</p>