Serum microRNAs as Tool to Predict Early Response to Benralizumab in Severe Eosinophilic Asthma.

José A Cañas,Joaquín Sastre,Manuel J Rial,Nicolás González-Mangado,Raquel García-Latorre,Mar Fernández-Nieto,Beatriz Sastre,Aida Gómez-Cardeñosa,Victoria Del Pozo,Marta Gil-Martínez,José M Rodrigo-Muñoz,Marcela Valverde-Monge,Erwin J Pinillos-Robles,María J Rodríguez-Nieto

doi:10.3390/jpm11020076

Abstract

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.

Highlights

Asthma is a chronic inflammatory disease of the airways that affects more than 300 million people worldwide [1]
It is worth noting that after eight weeks of treatment, severe asthmatics reduced, in a significant manner, the number of exacerbations and the eosinophil count, they did not improve lung function neither asthma control test (ACT) values (Table 1)
We observed in the asthmatic population that severe asthmatic patients at baseline had significant higher number of exacerbations, and lower FEV1 and ACT values than mild to moderate asthmatics (Table 1)

Summary

Introduction

Asthma is a chronic inflammatory disease of the airways that affects more than 300 million people worldwide [1] This pathology causes shortness of breath, chest tightness, wheezing and cough, and presents a strong inflammatory component related to T2 immune response [2]. This disease exhibits an elevated heterogeneity and variability, which means that it is an ineffective asthma control in many cases. Severe asthma comprises a small group of asthmatic individuals, between 5–10% of people with asthma who have a higher risk of severe exacerbation, clinical worsening and poor control Among these patients, an estimated 40–60% have eosinophilic airway inflammation, which is associated with severe asthma, despite high-inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) therapies [3].

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