NEW YORK (Reuters Health)—Early immune response signatures in the critically injured may shed light on mechanisms underlying multiple organ system failure, according to U.K. investigators.
As Dr. Joanna M. Shepherd of Queen Mary University of London tells Reuters Health by email, “Multiple organ dysfunction syndrome (MODS) is common after major trauma and it contributes to poor outcomes and death in many critically injured patients. Our research shows that key immune changes occur within the first few hours of injury that are associated with development of MODS.”
“This hyperacute timeframe is usually very difficult to study because of the logistical challenges of doing research in the emergency setting,” Dr. Shepherd adds.
In a July 17 online paper in PLOS Medicine, Dr. Shepherd and colleagues note that such studies thus “tend to focus on patients later in their clinical course, after widespread inflammation has already been established and after patients have been subjected to further surgery, drugs, and transfusions.”1
To help identify the early mechanisms “that then evolve into the full genomic storm,” the team studied critically ill patients in the hyperacute time period within two hours of injury, using whole blood transcriptome and flow cytometry analyses.
In 36 critically injured patients, the team examined 29,385 immune cell genes obtained within whole blood samples and compared these with samples taken at 24 and 72 hours following injury.
In 34 patients, the numbers of circulating immune cell populations were compared with those in healthy volunteers.
The researchers also compared the 20 critically injured patients who developed MODS with the 16 who did not, and with other patients with minor injuries.
Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients compared to healthy volunteers. By 24 hours, this was true of 6,294 transcripts (21%) but only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury.
Comparison of the MODS and non-MODS groups showed that 363 genes differed at admission but only 33 were expressed differentially in the MODS group at 24 hours and only 28 at 72 hours.
Thus, say the investigators, “The MODS signature is clearly set within the hyperacute window, and most of these genes either normalize or invert their levels of expression by 24 hours.”
Further analysis showed enrichment of gene pathways associated with cell death in the MODS group and implicated downregulation of neutrophils and upregulation of natural killer immune cells.
“Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity,” the researchers say.
Summing up, Dr. Shepherd concluded that the new work in the hyperacute phase “identifies this period as crucial for understanding how MODS develops after trauma. Our findings provide exciting opportunities for developing new therapies that help protect organs after major injury.”
Reference
- Cabrera CP, Manson J, Shepherd JM, et al. Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study. PLoS Med. 2017 Jul 17;14(7):e1002352. doi: 10.1371/journal.pmed.1002352. eCollection 2017 Jul.
