Circulating miR-29a as a new biomarker of food anaphylaxis and endothelial glycocalyx regulation

To the editor Background Anaphylaxis is an acute and potentially life-threatening hypersensitivity reaction often involving the cardiovascular system. Circulating microRNAs (miRNAs/miR), including those carried by extracellular vesicles (EVs), are emerging biomarkers that display regulatory functions in allergy. This study aims to investigate the role of miR-29a in anaphylaxis. Methods MiR-29a (3p and 5p) levels were assessed by qPCR from acute and baseline samples of serum and EVs from 70 patients with food- and drug-mediated anaphylaxis. EVs purification was confirmed by Western blot, electron microscopy, and NanoSight. MiR-29a-3p target genes were studied in silico using systems biology analysis (SBA). Moreover, miR-29a levels were evaluated in vitro in endothelial cells (ECs) exposed to anaphylactic mediators. Additionally, a panel of endothelial glycocalyx (eGCX)-associated mRNA was analyzed after transfection with a miR-29a-3p inhibitor. Results Patients with food-induced anaphylaxis exhibited reduced miR-29a-3p levels in both serum and EVs during the acute reaction. In contrast, miR-29a-5p levels were decreased in serum but not in EVs. No significant modulation of either miRNA was observed in drug-induced anaphylaxis. SBA of miR-29a-3p identified molecular pathways, biological processes and functional networks associated with eGCX remodelling. Intracellular levels of miR-29a-3p were modulated in vitro in ECs following exposure to anaphylactic mediators. Inhibition of miR-29a-3p significantly reduced ESM1 expression. Conclusions The miR-29a-3p levels are decreased in serum and EVs from patients with acute food-induced anaphylaxis, suggesting its potential as a promising biomarker. Moreover, a role for miR-29a-3p in eGCX integrity under anaphylactic conditions was demonstrated, potentially regulating ESM1 . Key Message MiR-29a-3p is selectively reduced in serum and extracellular vesicles during acute food-induced anaphylaxis and may regulate endothelial glycocalyx-related pathways, which supports its potential as a novel biomarker and molecular mediator of vascular involvement in anaphylactic reactions.