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Bioinformatics, Computational and Systems Biology

Omics II

Large trauma patient cohort reveals IL-29 as a novel responder to traumatic injury and predictor of survival

Saturday, October 26, 2024
3:30 PM – 3:45 PM EST
Location: Room 324

Introduction: 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.

Materials and

Methods: 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. The study was conducted in accordance with Good Clinical Practice, the principles of the Belmont Report, and HHS regulations enumerated under 45 CFR 46. De-identified samples and other data were included in the study through IRB-approved waivers of consent and authorization (Advarra Protocol # Pro00022129). 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. Samples were processed and tested on a custom 59-plex MesoScale Diagnostics electrochemiluminescence assay as per manufacturer’s instructions. Data were analyzed via Tobit Regressions and Random Forest modeling using R 4.2.x. Exploratory statistical analyses were completed in GraphPad Prism v10.2.2.

Results, Conclusions, and Discussions: 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. Interestingly, IL-10 and IL-29 share a receptor chain (IL-10RB) and have inverse relationships with patient survival, suggesting a potential mechanism of action through opposing forces on downstream signaling. Using machine learning via Random Forest, 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.

Acknowledgements (Optional): 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). Disclaimer: The contents of this publication are the authors' sole responsibility and do not necessarily reflect the views, opinions, or policies of the NIH, the Uniformed Services University of the Health Sciences, the Department of Health and Human Services (HHS), or the Department of Defense. Mentioning trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. This work was prepared by a military or civilian employee of the US Government as part of the individual’s official duties and therefore is in the public domain and does not possess copyright protection (public domain information may be freely distributed and copied; however, as a courtesy it is requested that the authors be given an appropriate acknowledgement).