House dust mite allergy (HDM) is of global importance and early sensitization is a predictive marker for persistent asthma. After exposure to allergens, an early asthmatic reaction (EAR) and sometimes a late asthmatic reaction (LAR) can occur. In patients with LAR, the relevance of mite exposure is much greater (1). For an clinician, to distinguishing between the two phenotypes is clinically difficult.

As part of the AMG study "Effects of tregalizumab on allergen-induced airway responses and airway inflammation in asthmatic patients" (Eudrac-CT number 2020-000585-41), 34 patients (age: median 26 (18 - 38) years) with mild asthma and HDM using bronchial allergen challenge (BAP) were investigated. MicroRNAs (miRNAs) were analyzed using next-generation sequencing (NGS) and a pathway enrichment analysis or protein-protein interaction network analysis was performed.

17 patients had a significant EAR (group 1) and 17 patients had a significant EAR + LAR (group 2), maximum FEV1 fall after BAP (EAR: group 1: 31.85 + 6.35% vs. Group 2 36.57 + 13.5% n.s) and (LAR: Group 1: FEV1 decrease 6.36 + 3.4% vs. Group 2: 31.7 + 10.29%; p < 0.0001). As expected, the patients with Group 2 showed a more pronounced asthmatic inflammation after 24 hours: Delta eNO Group 1: median 18 (-9-153) ppb vs Group 2 33 vs (18-113) ppb; FEV1 delta drop median group 1: 10 (-310-350) ml vs. 380 (-140-890) ml and delta eosinophils median 0.00 (-18-30) µ/L vs. 220 (6-420) ( µ/L). Interestingly, both groups could not be differentiated by the IgE, specific HDM IgE and/or the methacholine test.

NGS analysis showed a dysregulation in the expression of miR-15a/b-5p, miR-23-5p, miR-96-5p, miR-146a-5p, miR374a-5p and miR-378c. Network analysis revealed that these miRNAs play a role in Toll-like and T-cell receptor signaling as well as in TGF-β signaling.

Distinct miRNAs are potential biomarkers and could be used to diagnose LAR and future miRNA therapeutics

Reference: 1. Lopuhaä CE, et al Clin Exp Allergy. 2002;32(12):1720-7.