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 

TITLE=Computational Derivation of Core, Dynamic Human Blunt Trauma Inflammatory Endotypes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.589304

DOI=10.3389/fimmu.2020.589304

ISSN=1664-3224

ABSTRACT=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. 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 in the three survivor sub-groups suggested a role for type 3 immunity, in part regulated by Th17 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.