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Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes

Systemic inflammation ensues following traumatic injury, driving immune dysregulation and multiple organ dysfunction (MOD). While a balanced immune/inflammatory response is ideal for promoting tissue regeneration, most trauma patients exhibit variable and either overly exuberant or overly damped res...

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Autores principales: Schimunek, Lukas, Lindberg, Haley, Cohen, Maria, Namas, Rami A., Mi, Qi, Yin, Jinling, Barclay, Derek, El-Dehaibi, Fayten, Abboud, Andrew, Zamora, Ruben, Billiar, Timothy Robert, Vodovotz, Yoram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848165/
https://www.ncbi.nlm.nih.gov/pubmed/33537029
http://dx.doi.org/10.3389/fimmu.2020.589304
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author Schimunek, Lukas
Lindberg, Haley
Cohen, Maria
Namas, Rami A.
Mi, Qi
Yin, Jinling
Barclay, Derek
El-Dehaibi, Fayten
Abboud, Andrew
Zamora, Ruben
Billiar, Timothy Robert
Vodovotz, Yoram
author_facet Schimunek, Lukas
Lindberg, Haley
Cohen, Maria
Namas, Rami A.
Mi, Qi
Yin, Jinling
Barclay, Derek
El-Dehaibi, Fayten
Abboud, Andrew
Zamora, Ruben
Billiar, Timothy Robert
Vodovotz, Yoram
author_sort Schimunek, Lukas
collection PubMed
description Systemic inflammation ensues following traumatic injury, driving immune dysregulation and multiple organ dysfunction (MOD). While a balanced immune/inflammatory response is ideal for promoting tissue regeneration, most trauma patients exhibit variable and either overly exuberant or overly damped responses that likely drive adverse clinical outcomes. We hypothesized that these inflammatory phenotypes occur in the context of severe injury, and therefore sought to define clinically distinct endotypes of trauma patients based on their systemic inflammatory responses. Using Patient-Specific Principal Component Analysis followed by unsupervised hierarchical clustering of circulating inflammatory mediators obtained in the first 24 h after injury, we segregated a cohort of 227 blunt trauma survivors into three core endotypes exhibiting significant differences in requirement for mechanical ventilation, duration of ventilation, and MOD over 7 days. Nine non-survivors co-segregated with survivors. Dynamic network inference, Fisher Score analysis, and correlations of IL-17A with GM-CSF, IL-10, and IL-22 in the three survivor sub-groups suggested a role for type 3 immunity, in part regulated by Th17 and γδ 17 cells, and related tissue-protective cytokines as a key feature of systemic inflammation following injury. These endotypes may represent archetypal adaptive, over-exuberant, and overly damped inflammatory responses.
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spelling pubmed-78481652021-02-02 Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes Schimunek, Lukas Lindberg, Haley Cohen, Maria Namas, Rami A. Mi, Qi Yin, Jinling Barclay, Derek El-Dehaibi, Fayten Abboud, Andrew Zamora, Ruben Billiar, Timothy Robert Vodovotz, Yoram Front Immunol Immunology Systemic inflammation ensues following traumatic injury, driving immune dysregulation and multiple organ dysfunction (MOD). While a balanced immune/inflammatory response is ideal for promoting tissue regeneration, most trauma patients exhibit variable and either overly exuberant or overly damped responses that likely drive adverse clinical outcomes. We hypothesized that these inflammatory phenotypes occur in the context of severe injury, and therefore sought to define clinically distinct endotypes of trauma patients based on their systemic inflammatory responses. Using Patient-Specific Principal Component Analysis followed by unsupervised hierarchical clustering of circulating inflammatory mediators obtained in the first 24 h after injury, we segregated a cohort of 227 blunt trauma survivors into three core endotypes exhibiting significant differences in requirement for mechanical ventilation, duration of ventilation, and MOD over 7 days. Nine non-survivors co-segregated with survivors. Dynamic network inference, Fisher Score analysis, and correlations of IL-17A with GM-CSF, IL-10, and IL-22 in the three survivor sub-groups suggested a role for type 3 immunity, in part regulated by Th17 and γδ 17 cells, and related tissue-protective cytokines as a key feature of systemic inflammation following injury. These endotypes may represent archetypal adaptive, over-exuberant, and overly damped inflammatory responses. Frontiers Media S.A. 2021-01-18 /pmc/articles/PMC7848165/ /pubmed/33537029 http://dx.doi.org/10.3389/fimmu.2020.589304 Text en Copyright © 2021 Schimunek, Lindberg, Cohen, Namas, Mi, Yin, Barclay, El-Dehaibi, Abboud, Zamora, Billiar and Vodovotz http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Schimunek, Lukas
Lindberg, Haley
Cohen, Maria
Namas, Rami A.
Mi, Qi
Yin, Jinling
Barclay, Derek
El-Dehaibi, Fayten
Abboud, Andrew
Zamora, Ruben
Billiar, Timothy Robert
Vodovotz, Yoram
Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title_full Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title_fullStr Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title_full_unstemmed Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title_short Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes
title_sort computational derivation of core, dynamic human blunt trauma inflammatory endotypes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848165/
https://www.ncbi.nlm.nih.gov/pubmed/33537029
http://dx.doi.org/10.3389/fimmu.2020.589304
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