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Serum microRNAs catalog asthmatic patients by phenotype

Gil-Martínez Marta1, 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, 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)
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. Due to the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify patients and treat them properly with novel biologics. A promising tool for diagnosis are microRNAs (miRNAs).
Objective: The aim of this study was to find serum miRNAs that can phenotype asthmatic patients.
Material and Methods: Serum miRNAs of eosinophilic (N=40) and non-eosinophilic (N=36) asthmatic individuals were evaluated by next-generation sequencing (NGS), specifically miRNAs-seq, and selected miRNAs were validated by RT-qPCR. Pathways enrichment analysis of deregulated miRNAs was performed.
Results: NGS analysis revealed 15 differentially expressed miRNAs between eosinophilic and non-eosinophilic asthmatic patients, while did not show differences in the miRNome between atopic and non-atopic asthmatic individuals. Of the 15 differentially expressed miRNAs between eosinophilic and non-eosinophilic asthmatics, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these two miRNAs were higher in eosinophilic than in non-eosinophilic asthmatics. Furthermore, expression values of hsa-miR-26a-1-3p inversely correlated with peripheral blood eosinophil count and hsa-miR-376a-3p expression values with FeNO values and exacerbations number. Additionally, in silico pathway enrichment analysis revealed that these two miRNAs regulate signaling pathways related with asthma pathogenesis.
Conclusions: Hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to distinguish eosinophilic and non-eosinophilic asthmatic patients.

Key words: Asthmatic patients, Eosinophilic asthma, MicroRNA-seq, Phenotypes/Endotypes, Serum microRNAs