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Serum microRNAs Catalog Asthma Patients by Phenotype

Gil-Martínez M1, Rodrigo-Muñoz JM1,2, Sastre B1,2, Cañas JA1,2, García-Latorre R1, Redondo N1, de la Fuente L3, Mínguez P3,4, Mahíllo-Fernández I5, Sastre J2,6, Quirce S2,7, Caballero ML2,7, Olaguibel JM2,8, del Pozo V1,2,9

1Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
2Center for Biomedical Network of Respiratory Diseases (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
3Genetics and Genomics Department, Bioinformatics Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
4Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
5Biostatistics and Epidemiology Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
6Allergy Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
7Department of Allergy, Hospital Universitario La Paz, Madrid, Spain
8Allergy Unit, Complejo Hospitalario de Navarra, Navarra, Spain
9Universidad Autónoma de Madrid, Madrid, Spain

J Investig Allergol Clin Immunol 2022; Vol 32(6) : 471-478
doi: 10.18176/jiaci.0753

Background: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool.
Objective: The aim of this study was to identify serum miRNAs that can phenotype asthma patients.
Methods: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed.
Results: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma.
Conclusion: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Key words: Asthma patients, Eosinophilic asthma, microRNA-seq, Phenotypes/endotypes, Serum microRNAs