Novel mediator in anaphylaxis: decreased levels of miR-375-3p in serum and within extracellular vesicles of patients

Author:

Nuñez-Borque Emilio,Fernandez-Bravo Sergio,Rodríguez Del Rio Pablo,Palacio-García Lucia,Di Giannatale Angela,Di Paolo Virginia,Galardi Angela,Colletti Marta,Pascucci Luisa,Tome-Amat Jaime,Cuesta-Herranz Javier,Ibañez-Sandin María Dolores,Laguna José Julio,Benito-Martin Alberto,Esteban Vanesa

Abstract

IntroductionAnaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers.MethodsAcute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP.ResultsA total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p<.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels.DiscussionThese findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.

Funder

Instituto de Salud Carlos III

FundaciÓn de la Sociedad Española de Alergología e Inmunología Clínica

Comunidad de Madrid

Publisher

Frontiers Media SA

Subject

Immunology,Immunology and Allergy

Reference57 articles.

1. World allergy organization anaphylaxis guidance 2020;Cardona;World Allergy Organ J,2020

2. Diagnosis and management of anaphylaxis in precision medicine;Castells;J Allergy Clin Immunol,2017

3. Paediatric emergency department anaphylaxis: different patterns from adults;Braganza;Arch Dis Child,2006

4. Diagnosis and management of drug-induced anaphylaxis in children: An EAACI position paper;Atanaskovic-Markovic;Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol,2019

5. Time to revisit the definition and clinical criteria for anaphylaxis;Turner;World Allergy Organ J,2019

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3