Changes in Serum MicroRNAs after Anti-IL-5 Biological Treatment of Severe Asthma

Abstract

There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (p < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.

Keywords: anti-IL5 biologics; biomarkers; mepolizumab; microRNAs; reslizumab; severe asthma.

Figure 1

Anti-IL-5 biologics improved lung function and decreased peripheral eosinophils counts. Lung function (a) and peripheral eosinophil levels (b) were measured at baseline and an 8-week follow-up visit. After 8 weeks of mepolizumab or reslizumab drug administration, patients recovered their FEV₁ and lessened their peripheral eosinophils counts. *** p < 0.001, **** p < 0.0001.

Figure 2

Serum miRNA deregulation in severe asthmatic patients treated with anti-IL-5 drugs. Among the nine patients analyzed, five were severe asthmatics treated with mepolizumab and four with reslizumab. Eosinophilic asthmatic patients showed an altered expression of miR-195-5p, miR-27b-3p, miR-1260a, miR-423-3p, miR-193a-5p, and miR-338-3p at eight weeks after anti-IL-5 administration. Relative miRNA expression is expressed as 2^−ΔΔCt. * p < 0.05, ** p < 0.01.

Figure 3

Individual variation of miR-195-5p, miR-27b-3p, miR-1260a, miR-423-3p, miR-193a-5p, and miR-338-3p after 8 weeks of treatment. Relative expressions of these miRNAs were validated by RT-qPCR in serum samples from 16 asthmatic patients treated with mepolizumab or reslizumab. Among these miRNAs, miR-338-3p was the only one that modified its expression in a significant way. All experiments were performed in triplicate. Relative miRNA expression is expressed as 2^−ΔCt. Blue dots and lines represent patients treated with mepolizumab. Black dots and lines represent patients treated with reslizumab.