THE MARK COVENTRY AWARD: White Blood Cell Gene Expression

Abstract

We introduce a new genomic approach toward the study and diagnosis of infection. Our purpose is to show that synovial fluid white blood cells express a gene expression “signature” that differentiates septic from aseptic inflammation. Synovial fluid was aspirated from patients with acute Staphylococcus aureus infections or acute gout of the knee. Differential cell counts included predominantly neutrophils in all aspirates. Ribonucleic acid was isolated from the synovial-fluid white blood cells and was analyzed on the Affymetrix U133A GeneChip. The neutrophils from a patient whose knee is infected with Staphylococcus aureus can be distinguished from the neutrophils found in gout by nature of their differential gene expression. There are 1615 genes that have an expression level that is significantly different between the groups. The 124 most significant differences are in genes from immune pathways including the interleukin pathway, the tumor necrosis factor pathway, and the antibacterial response. The neutrophils at a site of infection (Staphylococcus aureus) express different genes than the neutrophils at a site of aseptic inflammation (gout). To our knowledge, this is the first in vivo demonstration of this principle. The differences in neutrophil gene expression may be used to develop simple laboratory tests that distinguish the causes of inflammation in a total joint arthroplasty. Level of Evidence: Diagnostic study, Level II-1. See the Guidelines for Authors for a complete description of levels of evidence.