Sepsis Research - Septicemia, Diagnosis, Symptoms, Treatment

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Gene expression profiles differentiate between sterile SIRS and early sepsis.

Johnson SB, Lissauer M, Bochicchio GV, Moore R, Cross AS, Scalea TM

R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. sbjohnson@umm.edu

INTRODUCTION: The systemic inflammatory response syndrome (SIRS) occurs frequently in critically ill patients and presents similar clinical appearances despite diverse infectious and noninfectious etiologies. Despite similar phenotypic expression, these diverse SIRS etiologies may induce divergent genotypic expressions. We hypothesized that gene expression differences are present between sepsis and uninfected SIRS prior to the clinical appearance of sepsis. METHODS: Critically ill uninfected SIRS patients were followed longitudinally for the development of sepsis. All patients had whole blood collected daily for gene expression analysis by Affymetrix Hg_U133 2.0 Plus microarrays. SIRS patients developing sepsis were compared with those remaining uninfected for differences in gene expression at study entry and daily for 3 days prior to conversion to sepsis. Acceptance criteria for differentially expressed genes required: >1.2 median fold change between groups and significance on univariate and multivariate analysis. Differentially expressed genes were annotated to pathways using DAVID 2.0/EASE analysis. RESULTS: A total of 12,782 (23.4%) gene probes were differentially expressed on univariate analysis 0 to 48 hours before clinical sepsis. 626 (1.1%) probes met acceptance criteria, corresponding to 459 unique genes, 65 (14.2%) down and 395 (85.8%) up expressed. These genes annotated to 10 pathways that functionally categorized to 4 themes involving innate immunity, cytokine receptors, T cell differentiation, and protein synthesis regulation. CONCLUSIONS: Sepsis has a unique gene expression profile that is different from uninfected inflammation and becomes apparent prior to expression of the clinical sepsis phenotype.

Published 6 April 2007 in Ann Surg, 245(4): 611-21.
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Sepsis Research Today Archive:

Volume 1 (2004)
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Sepsis Books

Sepsis: New Insights, New Therapies, Novartis Foundation Symposium (Novartis Foundation Symposia)

Sepsis: New Insights, New Therapies, Novartis Foundation Symposium (Novartis Foundation Symposia)