Background Injured patients show higher rates of mortality and multiple organ dysfunction syndrome (MODS) as the severity of their injury increases. This study aimed to investigate the relationship between anatomical injury severity and the immediate underlying biological response to injury, developing our understanding this response and providing insight into the physiological processes potentially driving poor clinical outcomes in trauma patients.

Method Prospectively collected data and samples from a cohort of 413 trauma patients recruited to the ACIT-II study (REC approval: 07/Q0603/29) were used. ISS was used to categorise patients into groups of increasing anatomical injury severity (ISS 0-3 = Control, ISS 4-8 = Mild, ISS 9-15 = Moderate, ISS 16-24 = Severe, ISS 25-35 = Critical, ISS ≥36 = Super Critical). Proteomics analysis for 4979 proteins was performed on blood samples taken at presentation to the ED. Median change from Control was calculated for each protein in each injury severity group. Those showing significant change were utilised for pathway analysis, identifying enriched biological processes associated with higher injury severity groups.

Results The number of proteins showing change from Control increases cumulatively as injury severity increases, with 3865 proteins showing significant change in the Super Critical group. 496 of these are unique to this group. A total of 2118 proteins show significant change in only the Critical and/or Super Critical groups. Pathway analysis on both the Super Critical group (ISS ≥36) and combined Critical-Super Critical (ISS ≥25) group identifies a large number of processes, with the JAK-STAT signalling pathway most significantly enriched in both analyses.

Conclusion The biological response to trauma is massive and complex, however proteomic pathway analysis of patients with the highest levels of injury can highlight areas for further investigation, supporting future work on the potential identification of modifiable targets within these pathways and the optimisation of personalised care for trauma patients.