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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-7848165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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