Inflammatory complications following major trauma appear to be associated with changes in gene expression that only occur in some patients, thus putting them at higher risk of developing serious or fatal complications such as major organ failure.
These findings, from a study conducted by John Storey of Princeton University, USA and colleagues as part of the US-based Inflammation and the Host Response to Injury Large-Scale Collaborative Research Program and published in this week's issue of the journal PLoS Medicine, will help scientists understand why some patients develop inflammatory complications of trauma, which are responsible for more than half of long-term trauma-related deaths, while others do not. The study will also help to identify new drug targets for future therapy.
The authors followed 168 patients for up to 28 days after they experienced blunt-force trauma and used a molecular biology tool (a DNA microarray) to determine gene expression patterns in leukocytes (a type of immune system cell) collected from multiple blood samples taken from each patient during the first few days after injury. Then the authors categorized patients according to the degree of each patient's clinical inflammatory response (based on a measure of multi-organ failure called the Marshall score) and developed a statistical method to associate the early changes in gene expression with clinical outcomes.
The authors found that a quarter of genes, including some genes responsible for initiating and driving immune and inflammatory responses, showed early expression changes between 40 to 80 hours post-injury that were particularly strongly associated with longer-term complications. These expression changes also provided the strongest discrimination between patient clinical outcomes.
However, because gene expression was measured for total blood leukocytes isolated from peripheral blood samples, some of the differential expression changes identified could be confounded by changes in individual leukocyte subpopulations.
The authors say: "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 continue: "The expression variation at the genomic level that we have characterized among patients may help to provide a more comprehensive set of drug targets and a means to identify relevant subsets of patients for which these may be effective."
The authors add: "Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions."
Funding: This research is supported in part by NIH grant U54 GM-62119 (PI: Ronald Tompkins). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Desai KH, Tan CS, Leek JT, Maier RV, Tompkins RG, et al. (2011) Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study. PLoS Med 8(9): e1001093. doi:10.1371/journal.pmed.1001093
Office of Communications