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Published on: December 3, 2017
Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers
Ingo J Banke1, Niko Stade2, Peter M Prodinger2
1Clinic of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany. ingo.banke@mri.tum.de.
Background:
Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. However, current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. To close this diagnostic gap, reliable (bio)markers display the most promising candidates. Antimicrobial peptides (AMPs) are part of the innate immune response towards microbial growth. Recently we could show significant intraarticular levels of human cathelicidin LL-37 and β-defensin-3 (HBD-3) with high diagnostic accuracy in PJI synovial fluid. Consequently, these promising biomarkers were evaluated in PJI synovial membrane and synoviocytes, which may significantly facilitate histological diagnosis of PJI to improve outcome of septic joint replacement.
Methods:
In this prospective single-center controlled clinical study (diagnostic level II), consecutive patients with total hip (THR) and knee (TKR) replacements were included undergoing primary arthroplasty (n = 8), surgical revision due to aseptic loosening (n = 9) and septic arthroplasty with coagulase-negative staphylococci (n = 8) according to the criteria of the Musculoskeletal Infection Society (MSIS). Semiquantitative immunohistochemical (IHC) analysis of LL-37, HBD-3 and HBD-2 in synovial membrane and isolated synoviocytes based on Total Allred Score (TS) and Immunoreactive Remmele and Stegner score (IRS) was performed. For statistical analysis, SPSS 26.0/R3.6.3 (p < 0.05) was used.
Results:
The AMPs LL-37 and HBD-3 were significantly elevated (up to 20×) in synovial membranes from PJI compared to aseptic loosening or primary arthroplasty. The area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 1.0 for both scores revealing excellent diagnostic accuracy. Isolated synoviocytes as cellular AMP source showed comparable results with a significant LL-37/HBD-3-increase up to 3 × in PJI. In contrast, local HBD-2 levels were negligible (p > 0.23) upon PJI with a lower diagnostic accuracy (AUC = 0.65) in analogy to our previous findings with synovial fluid.
Conclusions:
Our results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI.
Insights
Antimicrobial peptides (AMPs), specifically human cathelicidin LL-37 and beta-defensin-3 (HBD-3), show high accuracy for diagnosing periprosthetic joint infection (PJI). These AMPs in synovial membranes and cells offer a promising tool for histological PJI diagnosis.
Area of Science:
- Orthopedics and Infectious Disease Research
- Biomarker Discovery for Infection Diagnosis
- Immunology of Prosthetic Joint Infections
Background:
- Accurate diagnosis of periprosthetic joint infection (PJI) is critical for successful joint replacement surgery.
- Current diagnostic methods lack sufficient accuracy for chronic, low-grade PJI.
- Antimicrobial peptides (AMPs) are key components of the innate immune response to infection.
Purpose of the Study:
- To evaluate human cathelicidin LL-37 and beta-defensin-3 (HBD-3) as biomarkers in synovial membranes and synoviocytes for PJI diagnosis.
- To assess the diagnostic accuracy of these AMPs in histological samples.
- To improve the histological diagnosis of PJI and enhance patient outcomes.
Main Methods:
- Prospective single-center study including patients undergoing primary arthroplasty, aseptic loosening revision, and septic arthroplasty.
- Immunohistochemical analysis of LL-37, HBD-3, and HBD-2 in synovial membranes and isolated synoviocytes.
- Semiquantitative scoring (TS and IRS) and receiver operating characteristic (ROC) curve analysis for diagnostic accuracy.
Main Results:
- LL-37 and HBD-3 were significantly elevated (up to 20x) in PJI synovial membranes compared to controls.
- Both LL-37 and HBD-3 demonstrated excellent diagnostic accuracy (AUC=1.0) in ROC analysis.
- Isolated synoviocytes also showed increased LL-37/HBD-3 levels in PJI, with HBD-2 showing negligible levels and lower diagnostic accuracy.
Conclusions:
- AMPs, particularly LL-37 and HBD-3, are highly promising and specific biomarkers for the histological diagnosis of PJI.
- The findings support the use of AMPs in synovial membranes and cells to improve PJI diagnosis.
- This research contributes to better diagnostic strategies for septic joint replacement outcomes.
