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

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 in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha. 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 -values. A validation study of expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The mRNA levels were normalized to and expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines. was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients ( = 8.63E-08 and fold change of 2.22). In the qPCR validation study, expression levels were significantly higher in asthmatic patients than in controls ( < 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 expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients. These results indicate that 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, could play a role as a biomarker and pharmacogenetic factor in asthma.