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MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction
Ruth P Duecker1, Oguzhan Alemdar1,2, Andreas Wimmers1,2
1Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
Abstract:
A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.
Insights
MicroRNAs (miRNAs) like miR-15a-5p, miR-15b-5p, and miR-374a-5p are downregulated in house dust mite-allergic asthma patients experiencing late asthmatic reactions. This finding may help predict late asthmatic reactions after allergen exposure.
Area of Science:
- * Immunology and Respiratory Medicine
- * Molecular Biology and Genetics
Background:
- * Asthma patients with house dust mite (HDM) allergy often experience both early (EAR) and late asthmatic reactions (LAR), indicating more severe allergic inflammation.
- * MicroRNAs (miRNAs) are crucial regulators in asthma pathogenesis, influencing inflammatory responses.
Purpose of the Study:
- * To investigate the miRNA profile in mild asthma patients with HDM allergy following bronchial allergen provocation (BAP).
- * To identify specific miRNAs associated with the development of late asthmatic reactions (LAR).
Main Methods:
- * Seventeen patients with EAR/no LAR and 17 with EAR plus LAR were analyzed after BAP.
- * Next-generation sequencing (NGS) was used for miRNA profiling.
- * FEV1 (forced expiratory volume in 1 second) and eNO (exhaled nitric oxide) were measured.
Main Results:
- * Patients with EAR plus LAR exhibited more significant allergic inflammation and a greater drop in FEV1 after 24 hours.
- * NGS-miRNA analysis revealed significant downregulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p in patients with EAR plus LAR.
- * These downregulated miRNAs negatively correlated with eNO and maximum FEV1 decrease, and target genes involved in airway remodeling.
Conclusions:
- * Specific miRNAs, including miR-15a-5p, miR-15b-5p, and miR-374a-5p, are downregulated in HDM-allergic asthmatics with LAR.
- * These miRNAs and their targeted pathways are implicated in the inflammatory processes following allergen exposure.
- * The identified miRNA profile may serve as a predictive biomarker for late asthmatic reactions.
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