SYNOVIAL FLUID MICRORNA BIOMARKERS ENABLE ACCURATE DIAGNOSIS OF HIP AND KNEE PERIPROSTHETIC JOINT INFECTIONS

Aim The aim of this study was to discover and independently validate synovial fluid miRNAs as potential biomarkers of septic knee and hip revision TJRs. Method Synovial fluid (SF) samples from 173 patients undergoing septic and aseptic revision total joint replacement surgery (TJR) of the hip and knee and 6 osteoarthritic (OA) knees were analyzed. The samples were divided into a discovery group (40 samples, 50% septic) and a validation cohort (133 samples, 35% septic). Small RNA next-generation sequencing (NGS) screened miRNAs in the discovery samples, with reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirming NGS findings and validating results in the independent larger cohort. Logistic regression and cross-validation were applied to assess the diagnostic power of individual and combined miRNAs. Results NGS identified 132 miRNAs with significant differences (FDR<0.05) between septic and aseptic SF samples. Of these, 18 miRNAs were further analyzed by RT-qPCR in the independent cohort, with miR-223-3p and miR-338-5p showing the highest increases in septic SF (8- to 16-fold), and miR-151a-3p and miR-214-3p the most substantial reductions. To investigate the performance of multivariable models, logistic regression was performed by dividing the cohort into a 60% training and 40% test set, which improved performance compared to individual miRNAs (median AUC 0.96 for multivariable models). Subgroup analysis by joint type, gender, and SF sample preparation confirmed robust miRNA biomarker performance for PJI. Conclusions Cell-free miRNA levels in synovial fluid of septic hip and knee TJRs alter in response to infection, indicating immune cell activity in the joint. These miRNAs offer sensitive and specific pathogen-independent biomarkers, presenting potential clinical applications in diagnosis of hip and knee PJI.