Genomic Storm in White Blood Cells of Trauma Patients

Introduction and Background

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory anti-inflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

 

The website below contains the genomic and clinical data from the trauma patients and their respective controls, and is an open-access tool for the scientific community to explore the relationship between longitudinal whole blood leukocyte genomic expression and clinical attributes in severely injured trauma patients.

The data set is obtained from both 35 healthy subjects and 167 severely injured patients, ages 16-55, who experienced blunt trauma and required aggressive resuscitation, including blood products. The study attributes include:

• 167 patients
• 35 healthy subjects
• 7 clinical sites

• Patient blood samples taken 12 hours and days 1, 4, 7, 14, 21, 28 after injury
• Blood leukocyte genome wide expression (Affymetrix U133+ v2 GeneChip™)
• 15 clinical attributes, including demographics and outcomes


In addition, the 167 trauma patients were stratified into two groups based on their clinical trajectories and outcomes. A full description of the two groups is contained in the J Exp Med publication. Briefly, patients who experienced an Uncomplicated Recovery (n=55) were defined as having no multiorgan failure defined as a Marshall score < 6, and a Time to Recovery in less than 5 days. In contrast, a Complicated Recovery (n=41) was defined as those patients with Marshall scores > 6 and a Time to Recovery on or after day 14. For more information regarding study design, please refer to the original manuscript (
Xiao et al., JEM, 208(13):2581-2590, 2011.)

Results

The Human Genomic Response to Severe Traumatic Injury
An interactive website for exploring gene expression and clinical outcomes.

09/24/08: Coefficient of Variation, top 10%, 30 clusters 
12/02/08: 9 clusters and 30 sub-clusters as the order of time and time-course MOF 
03/06/09: 8 clusters and 30 sub-clusters as normal and complicated patient response
10/27/09: 30 clusters as normal/complicated/other patient response, TEST version

 

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