Multiplex cytokine analysis for the identification of novel potential synovial fluid biomarkers for periprosthetic joint infections

Injury. 2024 Aug;55(8):111659. doi: 10.1016/j.injury.2024.111659. Epub 2024 Jun 19.

Abstract

Introduction: Periprosthetic joint infections (PJIs) are a devastating complication of total hip (THA) and knee (TKA) arthroplasty. The use of novel techniques like multiplex cytokine analysis could contribute immensely to the identification of potential novel biomarkers.

Patients and methods: This is a single-centre study of patients that were treated with revision TKA, THA or hemiarthroplasty. Serum's white blood cells (WBCs), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and synovial fluid's WBCs, percentage of polymorphonuclear neutrophils (%PMNs) and CRP were measured. Proteomic analysis targeting the secreted cytokines in synovial fluid was conducted using a 73-plex assay panel. The results were statistically compared between the septic and aseptic cases and ROC analysis to establish the area under the curve (AUC), sensitivity and specificity of each biomarker.

Results: The study included 30 patients (18 revision THA cases; 3 conversion of hemiarthroplasty to THA and 9 revision TKA cases); 14 cases were considered infected, 1 likely infected and 15 not infected. The results showed statistically significant differences (p < 0.05) between infected and not infected cases in serum's ESR, CRP and synovial fluid's%PMNs, growth-regulated oncogene alpha (GROA), interleukin-8, interleukin-5, S100-A8/calprotectin and resistin (RETN) with AUCs of 0.75, 0.72, 0.95, 0.75, 0.72, 0.95, 0.83, 0.73, 0.75, 0.81 and 0.76 respectively.

Conclusions: In the present study, serum ESR and CRP as well as synovial %PMNs, GROA, IL-8, IL-5, calprotectin and RETN protein levels were identified as potential biomarkers. Further studies are needed to further investigate their diagnostic utility and optimal cut-off values.

Keywords: Biomarkers; Multiplex cytokine analysis; Periprosthetic joint infection.

MeSH terms

  • Aged
  • Arthroplasty, Replacement, Hip* / adverse effects
  • Arthroplasty, Replacement, Knee* / adverse effects
  • Biomarkers* / analysis
  • Biomarkers* / metabolism
  • Blood Sedimentation
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Cytokines* / analysis
  • Cytokines* / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prosthesis-Related Infections* / diagnosis
  • Prosthesis-Related Infections* / metabolism
  • Proteomics / methods
  • Reoperation
  • Sensitivity and Specificity
  • Synovial Fluid* / chemistry
  • Synovial Fluid* / metabolism

Substances

  • Biomarkers
  • Cytokines
  • C-Reactive Protein