Specific signatures of the immune mechanisms that lead to serious organ failure are evident in the hours immediately following injury, according to a study by Joanna Shepherd of Queen Mary University of London, UK, and colleagues, publishing in PLOS Medicine. Multiple Organ Dysfunction Syndrome (MODS) is a condition that involves failure of organ systems including lung, heart, kidney, and liver and is thought to be a result of an excessive immune response after traumatic injury. While the precise immune mechanisms leading to MODS are not fully understood, the hyperacute window after injury is thought to be a critical period for understanding these mechanisms and for potential intervention.
In a cohort of 70 critically injured patients at Royal Hospital London, Shepherd and colleagues investigated the early immune response signatures in whole blood samples obtained within 2 hours of injury, and at 24 hours and 72 hours following injury. The researchers characterized circulating immune cell populations, and analyzed expression of 29,385 immune cell genes (available for 36 critically injured patients). When comparing patients who developed MODS to patients who did not develop MODS, they found 363 genes that were different at admission, but by 24 hours postinjury, only 33 genes differed between the groups. Further analysis of this hyperacute timeline demonstrated enrichment of gene pathways associated with cell death in patients with MODS and implicated downregulation of neutrophils and upregulation of natural killer immune cells.
While the authors note that this study is limited by its small sample size, and that larger cohorts will be able to investigate the drivers of the hyperacute response and different MODS phenotypes in more detail, the finding of a specific early response that developed into widespread activation could eventually lead to improvement in treatment of severe injury: "The findings suggest multiple new directions for discovery research and hold opportunities for translation in diagnostics, clinical trial design, precision medicine, and novel therapeutic and management approaches."
CPC, DW, and MRB were funded by the National Institute for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and The London School of Medicine and Dentistry. This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council [grant number MR/L016311/1]. JM was funded in part by the NIHR [academic clinical fellowship]. JMS is funded by the Wellcome Trust and Department of Health [grant numbers 101012/Z/13/Z and HICFR7405]. HDT was funded by grants from Barts and The London Charity and the Royal College of Surgeons of England. MBP is funded by an MRC-DTP PhD fellowship in Translational Immunology [grant number 1797139]. The Centre for Trauma Sciences received funding from Barts Charity [grant number 753/1722]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
KB is a member of the Editorial Board of PLOS Medicine and served as guest editor on PLOS Medicine's Special Issue on Trauma.
Cabrera CP, Manson J, Shepherd JM, Torrance HD, Watson D, Longhi MP, et al. (2017) Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study. PLoS Med 14(7): e1002352. https://doi.org/10.1371/journal.pmed.1002352
Centre for Translational Bioinformatics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
Centre for Trauma Sciences, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
Department of Genetics, Evolution & Environment, University College London, London, United Kingdom
Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary
University of London, London, United Kingdom
Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom
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