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Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia

Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients wit...

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Autores principales: Menéndez, Rosario, Méndez, Raúl, Almansa, Raquel, Ortega, Alicia, Alonso, Ricardo, Suescun, Marta, Ferrando, Ana, Feced, Laura, Bermejo-Martin, Jesús F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780106/
https://www.ncbi.nlm.nih.gov/pubmed/31500177
http://dx.doi.org/10.3390/jcm8091404
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author Menéndez, Rosario
Méndez, Raúl
Almansa, Raquel
Ortega, Alicia
Alonso, Ricardo
Suescun, Marta
Ferrando, Ana
Feced, Laura
Bermejo-Martin, Jesús F.
author_facet Menéndez, Rosario
Méndez, Raúl
Almansa, Raquel
Ortega, Alicia
Alonso, Ricardo
Suescun, Marta
Ferrando, Ana
Feced, Laura
Bermejo-Martin, Jesús F.
author_sort Menéndez, Rosario
collection PubMed
description Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). Methods: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. Results: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. Conclusions. CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.
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spelling pubmed-67801062019-10-30 Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia Menéndez, Rosario Méndez, Raúl Almansa, Raquel Ortega, Alicia Alonso, Ricardo Suescun, Marta Ferrando, Ana Feced, Laura Bermejo-Martin, Jesús F. J Clin Med Article Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). Methods: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. Results: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. Conclusions. CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment. MDPI 2019-09-06 /pmc/articles/PMC6780106/ /pubmed/31500177 http://dx.doi.org/10.3390/jcm8091404 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Menéndez, Rosario
Méndez, Raúl
Almansa, Raquel
Ortega, Alicia
Alonso, Ricardo
Suescun, Marta
Ferrando, Ana
Feced, Laura
Bermejo-Martin, Jesús F.
Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title_full Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title_fullStr Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title_full_unstemmed Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title_short Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia
title_sort simultaneous depression of immunological synapse and endothelial injury is associated with organ dysfunction in community-acquired pneumonia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780106/
https://www.ncbi.nlm.nih.gov/pubmed/31500177
http://dx.doi.org/10.3390/jcm8091404
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