Abstract
INTRODUCTION:
The diagnosis of periprosthetic joint infection (PJI) remains a serious challenge. Based on previous work, we believe that biomarkers will become the mainstay of diagnosing PJI in the future. We report on completion of our 8 year comprehensive biomarker program, evaluating the diagnostic profile of the 15 most promising synovial fluid biomarkers.
METHODS:
Synovial fluid was prospectively collected from 99 patients being evaluated for infection in the setting of revision hip or knee arthroplasty. All synovial fluid samples were tested by immunoassay for 15 putative biomarkers that were developed and optimized specifically for use in synovial fluid. Sensitivity, specificity and receiver operating Characteristic (ROC) curve analysis were performed for all biomarkers.
RESULTS:
The MSIS criteria, including cultures, CRP, ESR, fluid WBC, PMN%, and histology, was used to classify 30 PJIs and 69 cases of aseptic failure. Four synovial fluid biomarkers (alpha-defensin, bactericidal/permeability increasing protein, neutrophil gelatinase-associated lipocalin, and resistin) correctly predicted the MSIS classification of all patients in this study, exhibiting an AUC of 1.0 with >98% sensitivity and specificity for the diagnosis of PJI. Eight other biomarkers exhibited an AUC of >0.9. These results all outperformed the tests for serum CRP (specificity 87%, sensitivity 96%) and ESR (specificity 80%, sensitivity 93%). Interestingly, the Pearson correlations comparing the biomarkers to each other and to the synovial fluid WBC in the group of infected samples revealed only weak correlations, demonstrating that these biomarkers are not simply inflammatory biomarkers.
DISCUSSION AND CONCLUSION:
A comprehensive biomarker program has led to the identification of several synovial fluid biomarkers that appear to be diagnostic for PJI. The four top biomarkers are proteins that have known functional roles in the cellular response to pathogens. These biomarkers outperform our currently utilized serum tests and can be used to develop rapid bedside immunoassays for PJI.
