649. Prospective Validation of an 11-mRNA Host Immune Signature as a Novel Blood Test for Acute Septic Arthritis

Abstract

Abstract Background Septic arthritis is an orthopedic emergency requiring immediate surgical intervention. Joint aspirations detect inflammatory cells within hours but often cannot distinguish between infections (e.g., bacterial) or other causes (e.g., gout). Cultures take days, so decisions about surgery are made with incomplete data. Aspirations carry risk and require technical skill and advanced imaging. Novel diagnostics are thus needed. An 11-mRNA host immune blood signature has been validated to distinguish between infectious and noninfectious acute inflammation. It is part of the 29-mRNA HostDx™ Sepsis test that can also distinguish between bacterial and viral infections and predicts severity (currently under development as a rapid point-of-care test). We studied whether the 11-mRNA signature can determine if acute arthritis was due to an infectious cause. Methods We conducted a blinded, prospective, noninterventional study on patients undergoing workup for a septic primary joint. Patients received standard-of-care including joint aspiration and lab tests: White Blood Cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and joint fluid analysis. Simultaneously, blood was drawn (PAXgene RNA tubes). mRNAs were measured on NanoString nCounter™ blinded to clinical results. Results 20 patients were included, of which 10 had infections based on positive synovial fluid cultures. The 11-mRNA blood signature had an area under the ROC curve (AUROC) of 0.87 for separating infectious from noninfectious conditions compared with 0.58 (ESR), 0.60 (CRP), and 0.50 (WBC); AUROC for synovial WBC was 0.54. At 100% sensitivity for infection, specificity of the signature was 40%; thus, a substantial fraction of nonseptic patients could have been ruled out for further surgical intervention. Conclusion The 11-mRNA signature showed markedly increased accuracy in predicting septic joints compared with routine diagnostic markers. As a quick point-of-care test this blood RNA signature may be an important tool for early, accurate identification of acute septic joints and need for emergent surgery, thereby improving clinical care and healthcare spending. These findings further add to the generalizability of results obtained in the HostDx Sepsis test. Disclosures All authors: No reported disclosures.