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Proteomic profile of extracellular vesicles in anaphylaxis and their role in vascular permeability
  • +11
  • Emilio Nuñez-Borque,
  • Sergio Fernandez-Bravo,
  • Carlos Pastor-Vargas,
  • Gloria Alvarez-Llama,
  • Maria Gutierrez-Blazquez,
  • Ebrahim Alwashali,
  • José Laguna,
  • Javier Dionicio,
  • Diana Betancor,
  • Victoria Villalobos,
  • Jaime Tome-Amat,
  • Javier Cuesta Herranz,
  • Alberto Benito-Martin,
  • Vanesa Esteban
Emilio Nuñez-Borque
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz

Corresponding Author:emilionunezb@quironsalud.es

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Sergio Fernandez-Bravo
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Carlos Pastor-Vargas
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Gloria Alvarez-Llama
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Maria Gutierrez-Blazquez
Universidad Complutense de Madrid Facultad de Farmacia
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Ebrahim Alwashali
Universidad Complutense de Madrid Facultad de Farmacia
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José Laguna
Hospital Central de la Cruz Roja
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Javier Dionicio
Hospital Central de la Cruz Roja
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Diana Betancor
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Victoria Villalobos
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Jaime Tome-Amat
Centro de Biotecnologia y Genomica de Plantas
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Javier Cuesta Herranz
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Alberto Benito-Martin
Weill Cornell Medicine
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Vanesa Esteban
Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz
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Abstract

Background: Anaphylaxis is the most severe manifestation of allergic disorders. Diagnostic and understanding of molecular mechanisms need to improve. Extracellular vesicles (EVs) play a key role in cellular communication offering new possibilities to unravel patient-based particularities. The aim of this study is to analyze the protein profile of anaphylaxis-derived EVs providing a resource of potential markers for anaphylactic reactions, and to characterize their molecular mechanisms. Methods: EVs were isolated from 86 plasma samples (collected from 43 patients) during the acute phase of anaphylaxis (AnEVs) and at their baseline (BEVs). For comparison, EVs were characterized and their protein patterns were analyzed by mass spectrometry-based quantitative proteomics (LC-MS/MS). System Biology Analysis (SBA) was applied to identify main canonical pathways and molecules involved. In addition, in vitro permeability assays based on EVs-endothelial cells (ECs) were performed. Results: Differential proteomic analysis performed in 10 EVs paired patients’ samples identified 1206 proteins of which 99 were modulated in the AnEVs signature. CDC42, Ficolin-2 and S100A9 enrichment was confirmed in a larger cohort of patients. SBA revealed diverse group of immune proteins as the main canonical pathways altered in AnEVs. Thus, leukocyte extravasation and granulocyte adhesion-diapedesis processes stand out. In addition, marked-EVs from anaphylactic patients were captured by ECs decreasing the resistance of human endothelial monolayers. Conclusion: Our findings identify for the first time a differential EVs pattern signature in anaphylaxis revealing a source of potential biomarkers. Furthermore, these vesicles could participate in altered immune molecular mechanisms and present a role increasing vascular permeability.
Jul 2021Published in Allergy volume 76 issue 7 on pages 2276-2279. 10.1111/all.14792