American Surgical Association
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Gene Expression Profiles Differentiate Between SIRS and Early Sepsis
Steven B. Johnson, MD*, Matthew Lissauer, MD*, Grant Bochicchio, MD, MPH*, Richard Moore, MD, PhD*, Alan Cross, MD, PhD*, Thomas Scalea, MD
R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD

OBJECTIVES Despite diverse infectious and non-infectious etiologies, the systemic inflammatory response syndrome (SIRS) appears clinically similar irrespective of initiating insult. Our objective was to determine if differential gene expression occurs prior to clinical detection in early infected SIRS (sepsis) compared to uninfected SIRS.
METHODS Critically ill uninfected SIRS patients were prospectively evaluated for development of clinical sepsis. Two groups: 1) Pre-septic SIRS (n=45) - SIRS patients with subsequent clinical sepsis; 2) Uninfected SIRS (n=45) - SIRS patients remaining uninfected. Daily whole blood was collected into Paxgene tubes with gene expression analysis by Affymetrix Hg_U133 2.0 Plus microarrays (54,613 probes/chip). Significance criteria for differentially expressed genes required >1.2 fold change between groups and p<0.05 on univariate (corrected for multiple comparisons) or multivariate analysis. Significant genes were functionally categorized by DAVID 2.0 methodology with EASE analysis (p<0.1) and annotated to Biocarta and Kegg pathways.
RESULTS 12,782 (23.4%) gene probes were differentially expressed between groups 0-48 hours before clinical sepsis. Of these, 626 (1.1%) probes representing 459 unique genes demonstrated >1.2 fold change and were significantly different between groups. These genes functionally categorized to 10 pathways significantly different between groups (table).
CONCLUSIONS Prior to clinical detection, gene expression profiles and pathways.can differentiate between sepsis and uninfected SIRS.
Pathway# Significant Genesp value
Innate Immunity
TLR Signaling
MAPK Signaling
8
13
0.0080
0.0738
Cytokine Receptors
IL 22SR Signaling
Cytokine-Cytokine Receptor Interaction
IL 1R Signal Transduction
4
14
5
0.0102
0.0242
0.0307
T Cell Differentiation
Interferon Signaling Chaperones
Th1/Th2 Differentiation
IL 12/STAT 4 Dependent Signaling
4
4
4
0.0296
0.0467
0.0533
Protein Synthesis Regulation
Apoptosis
eIF4e/p70 S6 Kinase Regulation
8
4
0.0104
0.0603


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