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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Bibliographic Details
Published in:	Frontiers in immunology Vol. 11; p. 589304
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 18-01-2021
Subjects:	biomarker critical illness Immunology inflammation network analysis systems biology systems biology network analysis biomarker critical illness inflammation
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Bhalchandra Mirlekar, University of North Carolina at Chapel Hill, United States; Antonio Riva, Foundation for Liver Research, United Kingdom Edited by: Antonio Cappuccio, Mount Sinai Hospital, United States This article was submitted to Inflammation, a section of the journal Frontiers in Immunology Present address: Andrew Abboud, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2020.589304