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The response to major physical trauma such as that sustained by people involved in serious car crashes varies widely; some patients will go into irreversible (fatal) organ failure about a week after the injuries were sustained, whilst others recover. Organ failure is a leading cause of death among trauma victims. A recent publication in Proceedings of the National Academy of Sciences (PNAS) reports the results of comparative genomic analysis intended to address why some patients die whilst others survive, something that clinicians are presently unable to predict.

A team of US scientists studied white blood cells (leukocytes) from a small group of severely injured patients with organ failure and healthy controls; these blood cells were chosen because they have been implicated in the inflammatory responses associated with the development of post-injury multiple organ dysfunction syndrome. The researchers found that severe trauma provoked alternative patterns of gene expression and the activation of different biological pathways, with the combined effect of reducing the activity of T-cells [Miller-Graziano C et al. (2006) PNAS 103(42):15564-9]. This prevents crucial T-cell regulation of the body’s immune response, so that the process becomes out of control and effectively destroys tissues and organs.

The authors propose that using genome-wide expression analysis combined with cell-type specific pathway analyses may be of value in revealing pathway alterations in other forms of disease. Study author Carol Miller-Graziano commented: “Our study proves for the first time that it is possible to identify the genetic and protein changes in specific immune cells that play a significant role in determining whether or not trauma is fatal…we believe that the techniques established here can provide insights into many disease that involve human immune system failure” (see press release).

Comment: This research is a step towards a prognostic tool that would allow clinicians to identify patients moving into organ failure, and by providing information about the pathological pathways involved in the process it also creates the possibility of developing protective interventions. A comparison of genetic responses from trauma patients who did not develop organ failure with those who did would have been an interesting additional component to the study. However, given that the expression of many thousands of different genes is altered following injury, these researchers used an intelligent approach based on what was already known about the biological processes involved in organ failure, to home in on the genetic changes in key cellular mediators.