Analysis of synovial biomarkers with a multiplex protein microarray in patients with PJI undergoing revision arthroplasty of the hip or knee joint

Arch Orthop Trauma Surg. 2020 Dec;140(12):1883-1890. doi: 10.1007/s00402-020-03388-5. Epub 2020 Mar 5.


Introduction: Diagnosing a (low-grade) periprosthetic joint infection (PJI) after hip or knee arthroplasty remains a diagnostic challenge. The aim of this study was to evaluate the utility of using a novel multiplex protein microarray system for synovial biomarkers in determining PJI in patients undergoing revision knee or hip arthroplasty.

Materials and methods: The individual synovial fluid levels of 12 cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, GM-CSF, TNF-α, and INF-γ) were analysed with a novel multiplex protein microarray system in 32 patients undergoing revision hip (n = 22) or knee (n = 10) arthroplasty. Cases were classified into septic and aseptic groups on basis of pre- and interoperative findings: [PJI (n = 14) vs. non-PJI (n = 18)]. Receiver operator characteristic (ROC) curves were calculated to assess the discriminatory strength of the individual parameters. A multiple regression model was used to determine the utility of using a combination of the tested cytokines to determine the infection status.

Results: The levels of all of the evaluated cytokines were significantly elevated in the PJI-group. Best sensitivity and specificity were found for IL-6, followed by IL-1b, IL-10, and IL-17. The multiple regression models revealed a combination of IL-2, IL-4, IL-5, IL6, lL-12, and GM-CSF to be associated with the best sensitivity (100%) and specificity (88.9%) for a cut-off value of 0.41, with a likelihood ratio of 9.0.

Conclusion: Analysis of individual synovial fluid cytokine levels showed both high sensitivity and high specificity in diagnosing PJI. A combined model using several cytokines showed even higher sensitivity and specificity in diagnosing PJI and could thus be a useful predictive tool to determine the probability of PJI in patients with a painful prosthesis.

Level of evidence: Diagnostic IV.

Keywords: Cytokine; Periprosthetic joint infection; Revision arthroplasty; Synovial fluid.

MeSH terms

  • Aged
  • Arthritis, Infectious / diagnosis
  • Arthritis, Infectious / metabolism*
  • Arthritis, Infectious / surgery
  • Arthroplasty, Replacement, Hip*
  • Arthroplasty, Replacement, Knee*
  • Biomarkers
  • Cytokines / metabolism*
  • Female
  • Hip Prosthesis / adverse effects
  • Humans
  • Knee Joint
  • Knee Prosthesis / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Prosthesis-Related Infections / diagnosis
  • Prosthesis-Related Infections / metabolism*
  • Prosthesis-Related Infections / surgery
  • Protein Array Analysis
  • ROC Curve
  • Sensitivity and Specificity
  • Synovial Fluid / metabolism*


  • Biomarkers
  • Cytokines