Gene expression changes result in inflammatory response in trauma
MedWire News: Inflammatory responses in critically injured trauma patients are associated with changes in gene expression in some patients, research shows.
Investigators identified numerous "relevant pathways and gene sets with a coordinated pattern of expression variation" in selected patients who experienced major blunt-force trauma.
The inflammatory changes place the trauma patients at higher risk for developing major complications, such as organ failure, write John Storey (Princeton University, New Jersey, USA) and colleagues in the open-access journal PLoS Medicine.
Infections, sepsis, and major organ failure contribute to 50% to 60% of late trauma mortality but there is limited understanding of the biological processes that result in these post-injury inflammatory complications. The researchers followed-up 168 blunt-force trauma patients for 28 days after initial injury. They examined gene expression patterns in leukocytes collected from samples taken in the first few days after the trauma using DNA microarrays.
Patients were characterized based on the degree of clinical inflammatory responses using a measure of multiorgan failure. In turn, the researchers modeled the early changes in gene expression with clinical outcomes.
Results showed that 25% of the genome showed changes in their expression approximately 40 to 80 hours after the trauma. These early expression changes were associated with longer-term post-injury complications, "captured by at least five dynamic co-expression modules of functionally related genes," according to the investigators.
For example, the early down-regulation of major histocompatibility compex (MHC)-class II genes and the upregulation of p38 MAPK signaling pathway were strongly correlated with longer-term post-injury complications.
"The MHC-II molecules are relevant to major organ failure because they present foreign antigens on the cell surface, which is essential for adaptive or innate immunity," report Storey and colleagues.
The p38 MAPK gene plays an important role in driving the inflammatory response to microbial products, endogenous danger signals, and pro-inflammatory cytokines. It does so by phosphorylating transcription factors, which results in the further expression of inflammatory mediators, explain the researchers.
"These findings potentially provide the most comprehensive picture of the gene expression response to trauma to date, thereby demonstrating the power of moving beyond candidate gene studies of this clinical condition," they write.
The expression variation at the genomic level may help to provide a set of drug targets and a means to identify subsets of patients in whom the drugs might be effective, say researchers.
By MedWire Reporters