PMID- 37965316
OWN - NLM
STAT- MEDLINE
DCOM- 20231116
LR  - 20240318
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Novel mediator in anaphylaxis: decreased levels of miR-375-3p in serum and within 
      extracellular vesicles of patients.
PG  - 1209874
LID - 10.3389/fimmu.2023.1209874 [doi]
LID - 1209874
AB  - INTRODUCTION: Anaphylaxis 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. METHODS: Acute (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. RESULTS: A 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. DISCUSSION: These 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.
CI  - Copyright (c) 2023 Nunez-Borque, Fernandez-Bravo, Rodriguez Del Rio, 
      Palacio-Garcia, Di Giannatale, Di Paolo, Galardi, Colletti, Pascucci, Tome-Amat, 
      Cuesta-Herranz, Ibanez-Sandin, Laguna, Benito-Martin and Esteban.
FAU - Nunez-Borque, Emilio
AU  - Nunez-Borque E
AD  - Department of Allergy and Immunology, IIS-Fundacion Jimenez Diaz, Universidad 
      Autonoma de Madrid (UAM), Madrid, Spain.
FAU - Fernandez-Bravo, Sergio
AU  - Fernandez-Bravo S
AD  - Department of Allergy and Immunology, IIS-Fundacion Jimenez Diaz, Universidad 
      Autonoma de Madrid (UAM), Madrid, Spain.
FAU - Rodriguez Del Rio, Pablo
AU  - Rodriguez Del Rio P
AD  - Allergy Department, Hospital Infantil Universitario Nino Jesus, Fundacion 
      Hospital Nino Jesus (HNJ), Instituto de Investigacion del Hospital de La Princesa 
      (IIS-P), Madrid, Spain.
FAU - Palacio-Garcia, Lucia
AU  - Palacio-Garcia L
AD  - Department of Allergy and Immunology, IIS-Fundacion Jimenez Diaz, Universidad 
      Autonoma de Madrid (UAM), Madrid, Spain.
FAU - Di Giannatale, Angela
AU  - Di Giannatale A
AD  - Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesu 
      Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 
      Rome, Italy.
FAU - Di Paolo, Virginia
AU  - Di Paolo V
AD  - Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesu 
      Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 
      Rome, Italy.
FAU - Galardi, Angela
AU  - Galardi A
AD  - Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesu 
      Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 
      Rome, Italy.
FAU - Colletti, Marta
AU  - Colletti M
AD  - Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesu 
      Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 
      Rome, Italy.
FAU - Pascucci, Luisa
AU  - Pascucci L
AD  - Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
FAU - Tome-Amat, Jaime
AU  - Tome-Amat J
AD  - Centro de Biotecnologia y Genomica de Plantas, Universidad Politecnica de 
      Madrid-Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria 
      (UPM-INIA), Universidad Politecnica de Madrid, Madrid, Spain.
FAU - Cuesta-Herranz, Javier
AU  - Cuesta-Herranz J
AD  - Department of Allergy. Fundacion Jimenez Diaz University Hospital, Universidad 
      Autonoma de Madrid (UAM), Madrid, Spain.
FAU - Ibanez-Sandin, Maria Dolores
AU  - Ibanez-Sandin MD
AD  - Allergy Department, Hospital Infantil Universitario Nino Jesus, Fundacion 
      Hospital Nino Jesus (HNJ), Instituto de Investigacion del Hospital de La Princesa 
      (IIS-P), Madrid, Spain.
FAU - Laguna, Jose Julio
AU  - Laguna JJ
AD  - Allergy Unit, Allergo-Anaesthesia Unit, Cruz Roja Central Hospital, Villanueva de 
      la Canada, Madrid, Spain.
AD  - Faculty of Medicine and Biomedicine, Universidad Alfonso X el Sabio (UAX), 
      Madrid, Spain.
FAU - Benito-Martin, Alberto
AU  - Benito-Martin A
AD  - Faculty of Medicine and Biomedicine, Universidad Alfonso X el Sabio (UAX), 
      Madrid, Spain.
FAU - Esteban, Vanesa
AU  - Esteban V
AD  - Department of Allergy and Immunology, IIS-Fundacion Jimenez Diaz, Universidad 
      Autonoma de Madrid (UAM), Madrid, Spain.
AD  - Faculty of Medicine and Biomedicine, Universidad Alfonso X el Sabio (UAX), 
      Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231030
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (MicroRNAs)
RN  - 0 (Circulating MicroRNA)
RN  - 0 (Biomarkers)
RN  - 0 (MIRN375 microRNA, human)
SB  - IM
MH  - Adult
MH  - Child
MH  - Humans
MH  - *Anaphylaxis/genetics/metabolism
MH  - *MicroRNAs/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - *Circulating MicroRNA/metabolism
MH  - Biomarkers/metabolism
PMC - PMC10642912
OTO - NOTNLM
OT  - anaphylaxis
OT  - biomarker
OT  - endothelial permeability
OT  - extracellular vesicles
OT  - miRNA
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/11/15 06:43
MHDA- 2023/11/16 06:45
PMCR- 2023/01/01
CRDT- 2023/11/15 04:24
PHST- 2023/06/02 00:00 [received]
PHST- 2023/10/13 00:00 [accepted]
PHST- 2023/11/16 06:45 [medline]
PHST- 2023/11/15 06:43 [pubmed]
PHST- 2023/11/15 04:24 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1209874 [doi]
PST - epublish
SO  - Front Immunol. 2023 Oct 30;14:1209874. doi: 10.3389/fimmu.2023.1209874. 
      eCollection 2023.