Differentiating Infection from Aseptic Loosening: Analysis of Synovial Fluid Gene Expression Patterns

We have previously demonstrated that white blood cells aspirated from patients with Staphylococcus aureus–infected knees have a gene expression pattern that is dramatically different than patients with gout of the knee. The purpose of this study is to apply this new concept in distinguishing infected total knee arthroplasties from aseptically loose total knee arthroplasties. Synovial fluid was aspirated from patients with a total knee arthroplasty undergoing surgical intervention for acute infection or aseptic loosening. Patients with acute infection had elevated synovial fluid white blood cell counts (>5000), elevated ESR, elevated CRP, and positive bacterial cultures. Patients with aseptic loosening had low synovial fluid cell counts (<3000), loose components, and low clinical suspicion of infection. Ribonucleic acid was isolated from the synovial fluid white blood cells and was analyzed on the Affymetrix U133Aplus2 GeneChip. The white blood cells from patients with infection have a gene expression pattern that is different from that of patients with aseptic loosening. There are 2461 genes that have an expression level that is significantly different between the groups. These genes fall into families with common function and corresponded to the gene profile found to differentiate infection from gout in a previous study. These gene families include interleukins, antibacterial peptides, the defense response, and the toll receptor bacterial detection family. Synovial white blood cells are responsive cells that exhibit specific gene expression patterns during infection, differentiating them from the cells in aseptic conditions. With further study, inexpensive synovial fluid tests with a high sensitivity and specificity for infection could be developed.