A genomic storm in critically injured humans

TLDR

Human survival after injury depends on an appropriate inflammatory and immune response. The study characterizes the circulating leukocyte transcriptome after severe trauma, burn injury, and low‑dose endotoxin, revealing a global genomic storm that informs a new paradigm for the human immunological response to severe injury. Complications such as infections and organ failure vary only in the magnitude and duration of the genomic storm, and the shared gene‑expression patterns across injuries indicate a fundamental, common human response to severe inflammatory stress.

Abstract

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, 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 antiinflammatory 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.