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01-12-2020 | Joint Infection | Research

Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers

Authors: Ingo J. Banke, Niko Stade, Peter M. Prodinger, Jutta Tübel, Alexander Hapfelmeier, Rüdiger von Eisenhart-Rothe, Martijn van Griensven, Hans Gollwitzer, Rainer Burgkart

Published in: European Journal of Medical Research | Issue 1/2020

Abstract

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.

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Title: Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers
Authors: Ingo J. Banke
Niko Stade
Peter M. Prodinger
Jutta Tübel
Alexander Hapfelmeier
Rüdiger von Eisenhart-Rothe
Martijn van Griensven
Hans Gollwitzer
Rainer Burgkart
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Joint Infection
Biomarkers
Published in: European Journal of Medical Research / Issue 1/2020
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-020-00434-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Antimicrobial peptides in human synovial membrane as (low-grade) periprosthetic joint infection biomarkers

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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