Novel Biomarkers for Diagnosing Periprosthetic Joint Infection from Synovial Fluid and Serum

Abstract

Background: Synovial fluid bacterial culture is the cornerstone of confirmation or exclusion of periprosthetic joint infection (PJI). The aim of this study was to assess synovial fluid and serum biomarker patterns of patients with total joint arthroplasty (TJA), and the association of these patterns with PJI.

Methods: Synovial fluid and serum samples were collected from 35 patients who were admitted to the Arthroplasty Unit of the Department of Orthopaedics and Traumatology at Turku University Hospital. Of the 25 patients who were included in the study, 10 healthy patients with an elective TJA for osteoarthritis served as the control group, and 15 patients who were admitted due to clinical suspicion of PJI with local redness, swelling, wound drainage, pain, and/or fever and who had a positive synovial fluid bacterial culture served as the study group. Logistic regression was used to assess the ability of 37 biomarkers (including cytokines, chemokines, and growth factors) with commercially available tests to detect PJIs.

Results: In synovial fluid, the concentrations of sTNF-R1 and sTNF-R2 (soluble tumor necrosis factor receptors 1 and 2) and BAFF (B-cell activating factor, also known as TNFSF13B) were significantly higher in the PJI group (p < 0.002). In serum, the sTNF-R1 concentration was significantly higher in the PJI group, whereas the TWEAK (tumor necrosis factor-like weak inducer of apoptosis) and osteocalcin concentrations were significantly lower (p < 0.002). The sensitivity for detecting PJI using synovial fluid was 1.00 for sTNF-R2, 0.93 for sTNF-R1, and 0.87 for BAFF/TNFSF13B. The specificity of all 3 synovial markers was 1.00. The sensitivity using serum was 0.80 for TWEAK, 0.73 for sTNF-R1, and 0.80 for osteocalcin. The specificity of all 3 serum markers was 1.00.

Conclusions: Synovial sTNF-R2 is a promising new biomarker for detecting PJI. We are not aware of any previous reports of the use of sTNF-R2 in PJI diagnosis. More research is needed to assess the clinical importance of our findings.

Level of evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Fig. 1

The significance of differences in synovial fluid and serum biomarker concentrations (pg/mL) between the study and control groups, expressed as −log₁₀(p). The p value is from the Mann-Whitney U test. Larger bars indicate a larger difference, and only biomarkers with p < 0.1 are shown. Bars with a black dot correspond to differences for which the p value would remain significant after a Benjamini-Hochberg correction for the false discovery rate (FDR). + indicates that the biomarker had a larger concentration in the PJI group compared with the control group, while − indicates the opposite. The blue vertical line corresponds to p = 0.05, and the red line corresponds to the Bonferroni significance level of p = 0.002.

Fig. 2

Box plots comparing the concentrations of the 9 most promising synovial biomarkers between the PJI and control groups. For clarity, the natural logarithms of the biomarker concentrations are plotted. The boxes indicate the interquartile range (IQR), the horizontal line within a box indicates the median, and the whiskers indicate points closer to the box than 1.5 times the IQR width.

Fig. 3

Box plots comparing the concentrations of the 3 most promising serum biomarkers between the PJI and control groups. For clarity, the natural logarithms of the biomarker concentrations are plotted. The boxes indicate the interquartile range (IQR), the horizontal line within a box indicates the median, and the whiskers indicate points closer to the box than 1.5 times the IQR width.

Fig. 4

Receiving operating characteristic (ROC) curves for the 9 most promising synovial biomarkers.

Fig. 5

Receiving operating characteristic (ROC) curves for the 3 most promising serum biomarkers.