Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, as well as a new biomarker predictor of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types. Trauma patients had significantly upregulated proteins associated with immune activation (IL-23, MIP-5), immunosuppression (IL-10) and pleiotropic cytokines (IL-29, IL-6). A high ratio of IL-29 to IL-10 was identified as a new predictor of survival with ROC area of 0.933. Using machine learning, we identified three increased proteins (MIF, TRAIL, IL-29) and three decreased proteins (IL-7, TPO, IL-8) that were the most important in distinguishing a trauma blood profile from those of healthy controls. Biologic sex altered phenotype with IL-8 and MIF being lower in healthy women, but higher in female trauma patients when compared to male counterparts. This work identifies new responses to injury that may influence systemic immune dysfunction, serving as targets for therapeutics and immediate clinical benefit in identifying at-risk patients.

The authors have declared no competing interest.

This work was funded by the intramural research programs of the National Institute of Biomedical Imaging and Bioengineering, and National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with Good Clinical Practice, the principles of the Belmont Report, and HHS regulations enumerated under 45 CFR 46. Five of the sites had the Chesapeake/Advarra Institutional Review Board as the central IRB (Advarra Protocol # Pro00022129), and the Jacksonville, FL site had the University of Florida Institutional Review Board as the IRB of record. De-identified healthy volunteer blood samples were collected under clinical protocol NCT0000128 and NIH IRB-approved protocol 99-CC-0168 at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.

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Data and abbreviated clinical information will be made available in supplement after peer review. Not all detailed clinical information gathered during the study will be made available to prevent de-identification of samples and participants. Some values may be changed to ensure privacy of data while maintaining ability to complete any necessary meta-analyses.