Trauma Immunology

The human body’s response to injury is complex and vital to survival. Despite life saving resuscitation in the Emergency Department, severe blood loss through traumatic injury can lead to the dysfunction of vital organs (i.e. kidney, lung, heart, liver, brain). Approximately 30% of trauma patients who survive the first 48 hours will develop multiple organ dysfunction (MODS). This figure rises rapidly as the degree of haemorrhage and shock increases.

Our research indicates that MODS is linked to immune system dysregulation and immunosuppression with subsequent recurrent infections.The Organ Failure & Protection research theme is investigating the nature of the systemic immune- inflammatory response to trauma using gene expression profiling of blood samples taken from trauma patients.  Understanding the immune response to severe injury, from initial drivers to eventual outcomes, is crucial for improving patient outcomes.

The role of Gene Expression

Previous studies looking at the 24-72hr post injury window have shown a complex and widespread immune cell response termed the ‘genomic storm’, with both pro- and anti-inflammatory patterns.  The activators of this response are generated by extensive injury-induced immunogenic cell death and include damage-associated molecular patterns (DAMPs or alarmins) that are both passively and actively released by damaged or dying cells.  Understanding such a huge response is difficult, but the potential to trace the cascade of immune responses back towards the point of injury opens up the possibility of identifying early targets for pathway modulation, influencing the clinical trajectory and outcomes for each patient.

In order to look at this early window, we have previously performed pilot work using samples taken from trauma patients within 2 hours of injury (hyper-acute).  Whole blood transcriptomic analyses of these samples displayed a focused activation of damage recognition-associated innate immune cell pathways, while flow cytometry also revealed increased neutrophils, monocytes, NK cells, and innate lymphocytes such as γδ T cells.  Importantly, this study also revealed that almost the entire differential response associated with subsequent MODS (vs. noMODS) was present in the hyper-acute window and the hyper-acute response in patients who later developed MODS was markedly different to the response in individuals who did not get MODS, or indeed to patients with MODS at later time-points.

The results of our pilot work suggest that differential responses to severe injury in some individuals may lead to adverse clinical outcomes, however they do not rule out the possibility that patients who develop MODS may do so because they were more severely injured in the first place.  This highlights the difficulty of assessing injury severity using ISS as this anatomically based system may not be a good reflection of physiological injury burden related to the extent of actual tissue damage. 

Going forward, we will build on our previous work by attempting to answer a number of key outstanding questions. Crucially, are there differential immune responses to severe injury in the hyper-acute window that lead to distinct, and potentially unfavourable, clinical outcomes (e.g. MODS, infection)?  Furthermore, can biomarkers (and potential modifiable targets) of subsequent adverse clinical outcomes be identified in the hyper-acute window?  We will expand the transcriptomic analyses performed in our pilot study to a much larger cohort of trauma patients in order to further establish the presence of signatures related to patient outcomes.  Analysing hyper-acute samples from the same cohort of patients, we will look for patterns of immune mediators and DAMPS (as objective indicators of tissue damage) that may relate to the physiological burden of injury.  Using these results, we aim to clarify whether trauma-induced immune dysregulation is simply a consequence of surpassing an injury threshold, or instead represents a non-physiological response to severe injury occurring only in certain individuals.  We will also aim to identify drivers and potential modifiable targets of immune dysregulation leading to MODS with the eventual target of improving clinical outcomes for patients affected by severe injury.


Senior researcher: Dr Jennifer Ross


Share this page