Abstract
BackgroundSafe 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.MethodsIn 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.ResultsThe 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.ConclusionsOur results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI.
Highlights
Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty
With Human cathelicidin (LL-37) a clearly visible enhanced red dyeing in patients with septic arthroplasty group (SL) compared to aseptic loosening (AL) and primary arthroplasty group (PA) was obvious (Fig. 1)
Comparable results were obtained with Human β-defensin-3 (HBD-3) showing an obviously enhanced red dyeing in patients with SL compared to AL and PA
Summary
Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. Current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. 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. 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. The number of septic revision arthroplasties rises as well and the economic burden of periprosthetic joint infection (PJI)-related surgical interventions grows considerably [1, 3, 4]. The increase of morbidity, patientspecific risk factors and complexity of revision procedures are thought to be responsible [4]
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