Author Interviews, Genetic Research, Infections / 25.10.2014
Genetic Signature Provides Early Prediction of Sepsis and Organ Failure
MedicalResearch.com Interview with:
Dr R.E.W. (Bob) Hancock, OC, OBC, FRSC
{Canada Research Chair and Professor, Department of Microbiology and Immunology,UBC}
Director, Centre for Microbial Diseases and Immunity Research
University of British Columbia,
Vancouver, British Columbia, Canada
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Hancock: We wanted to understand how patients transitioned from the hyperinflammatory phase (cytokine storm) of sepsis to the hypoinflammatory (immunosuppressive) phase of sepsis (inability to respond appropriately to infections). About 15% of patients die in this first phase and 20% in the second phase, making sepsis one of the most deadly syndromes (35% overall mortality, 5 million deaths [8.3% of all deaths] annually worldwide). We hypothesized that immunosuppression was characterized by a state termed endotoxin tolerance a cellular amnesia (termed cellular reprogramming) in which cells fail to respond to microbial cues.
Overall we found that an Endotoxin Tolerance gene signature is significantly associated with the subsequent development of confirmed sepsis and new organ dysfunction in patients who had suspected sepsis. All 620 sepsis patients in retrospective and new analyses presented with an expression profile strongly associated with the endotoxin tolerance signature (p<0.01; AUC 96.1%). This occurred in fact very early in sepsis and in a new clinical study we found that the signature could be detected already in the emergency ward at first clinical presentation and 24-48 hours prior to definitive diagnosis. Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction.
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