A meta-analysis of synovial biomarkers in periprosthetic joint infection: Synovasure™ is less effective than the ELISA-based alpha-defensin test

Ahmad, Sufian S.; Hirschmann, Michael T.; Becker, Roland; Shaker, Ahmed; Ateschrang, Atesch; Keel, Marius; Albers, Christoph E.; Buetikofer, Lukas; Maqungo, Sithombo; Stöckle, Ulrich; Kohl, Sandro

doi:10.1007/s00167-018-4904-8

Cited by 46 publications

(35 citation statements)

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“…For example, the combination of synovial fluid AD measured by ELISA method and CRP test has demonstrated sensitivity of 97% and specificity of 100% for diagnosis of PJI [4]. Some additional, detailed studies dealing with the testing of synovial AD by ELISA have been published (e.g., in the work of Deirmengian et al [1,5], Bonanzinga et al [13], and Ahmad et al [24]), with all reporting sensitivity and specificity of the test in the range of 97-100%. As reported by Ahmad et al from a study based on meta-analysis of synovial biomarkers in PJI, the measurement of AD by ELISA in several respects outperforms that of the Synovasure ® lateral flow device [24].…”

Section: Discussionmentioning

confidence: 99%

“…Synovial fluid AD seem to be the most reliable biomarkers that could be used in a perioperative test for the diagnosis of PJI. While to date the qualitative lateral flow test and the quantitative ELISA test for AD determination have been used, to our knowledge, and regrettably, only a few comparative studies about their performance have been reported [12,15,24]. It must also be stressed that none of those studies is concerned about the proportion of individual α-defensins in the synovial fluid samples.…”

Section: Discussionmentioning

confidence: 99%

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High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defensins in Synovial Fluid for Diagnosis of Orthopedic Infections

et al. 2020

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The α-defensins (AD) present in synovial fluid have been regarded as constituting the most accurate periprosthetic joint infection (PJI) biomarker. The methods most commonly used for estimating AD as a biomarker are the qualitative Synovasure® PJI tests, based on the technique of lateral flow, and quantitative enzyme-linked immunosorbent assay (ELISA). Here, we propose a novel test based on detecting α-defensins in synovial fluid by high-performance liquid chromatography (HPLC). Synovial fluid was collected from 157 patients diagnosed with PJI, infectious arthritis (IA), arthrosis, reactive arthritis, and rheumatoid arthritis. AD concentrations in the fluid were determined by HPLC, and these same samples were used for additional diagnostic analyses. The results were statistically processed to calculate cutoff concentrations for PJI and IA. HPLC testing showed a sensitivity of 94% and a specificity of 92% for diagnosis of PJI, and a sensitivity of 97% and a specificity of 87% for diagnosis of IA. Using HPLC, we detected in synovial fluid a combination of three α-defensins: human neutrophil peptides HNP1, HNP2, and HNP3. All measured AD concentration values shown in this work refer to the sum of these three individual concentrations. Our study shows that the HPLC method meets the conditions for measuring precise concentrations of the sum of AD and can be recommended as part of a diagnostic array for PJI and IA diagnostics. By this method, we have verified that higher levels of AD in synovial fluid can also be seen in rheumatoid illnesses, crystal arthropathies, and reactive arthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defensins in Synovial Fluid for Diagnosis of Orthopedic Infections

et al. 2020

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“…The Synovasure kit is a qualitative test with the striking advantage of being a point‐of‐care assay, performed intra‐operatively. However, in addition to being quite expensive, recent meta‐analysis showed that its sensitivity for the detection of PJIs in a real setting is lower than expected, 15–17 possibly due also to the test being performed by untrained personnel. In contrast, the low‐cost HNPs MALDI‐TOF MS assay requires shipping of the sample to the laboratory and is performed by experienced personnel, but still it has a short turn‐around time (TAT; as described above) which is theoretically compatible with an intra‐operative setting, just planning and coordinating the surgery with the clinical laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of meta‐analyses, focused on the different performance of these two analytical methods, have been published. The immunoassay for α‐defensin in SF has been reported to have the highest sensitivity (97.3–100%) and specificity (95.5–100%) compared with other single biomarkers of PJIs, 12,13 whereas the lateral flow test presents a lower sensitivity, ranging from 71% to 92.1%, and specificity from 89% to 100% 15–18 …”

Section: Introductionmentioning

confidence: 99%

Detection of α‐defensin in synovial fluids by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry as an innovative and cost‐effective assay for improved definition of periprosthetic joint infections

Petrucca

Santino

Gentile

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale:Detection of α-defensins in synovial fluid is gaining more and more interest in the field of correct diagnosis of periprosthetic joint infections (PJIs). At present, they can be assessed by a quantitative enzyme-linked immunosorbent assay which is expensive and time-consuming and by a qualitative lateral flow immunoassay which is rapid but quite expensive and whose clinical sensitivity is debated. Thus, developing an alternative rapid, accurate, and low-cost assay for α-defensins is important to make α-defensins actionable as novel key clinical markers. Methods: Synovial fluid (SF) samples were obtained from 18 patients undergoing revision of primary joint arthroplasty. Of these, eight met the 2013 Musculoskeletal Infection Society (MSIS) criteria for PJIs, the remaining were classified as aseptic failure. Microbiological analysis and Synovasure assays were carried out on all samples. Sample preparation and the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) settings were adjusted to detect human neutrophil peptide (HNP)-1, -2 and -3 and to obtain optimal results in term of sensitivity and stability. Results: MALDI-TOF MS was able to detect HNPs in SF from septic patients. No signals for HNPs were detected in SF from aseptic failure. The limits of detection (LOD) were 2.5 and 1.25 μg/mL for HNP-2 and HNP-1, respectively. The turnaround time of the analysis is 20 min, and SF samples are stable at −20 C for up to 3 days.Assay sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 100% for all parameters. On the same SF samples, the Synovasure assay showed lower sensitivity specificity, and PPV and NPV of 87.5%, 90%, 87.5% and 90%, respectively. Microbiological analysis of SF confirmed the presence of bacteria only in SF MSIS-positive patients. Conclusions:The reported MALDI-TOF MS assay was able to detect and differentiate HNPs in SF samples and showed a slightly better diagnostic accuracy than the Synovasure assay.

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“…In the course also the synovial fluid AMP α-defensin has been proven to have excellent diagnostic accuracy in the detection of PJI up to a commercially available test since 2 years [29]. In multicenter studies, AMPs have been shown to outperform classical synovial fluid parameters such as WBC, CRP, percent segmented neutrophils and erythrocyte sedimentation rate [29,30]. Their capacity for PJI detection has been shown to be independent of prior antibiotic treatment, synovial fluid blood contamination, immunosuppression or natural skin flora.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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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A meta-analysis of synovial biomarkers in periprosthetic joint infection: Synovasure™ is less effective than the ELISA-based alpha-defensin test

Abstract: III.

Cited by 46 publications

References 44 publications

High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defensins in Synovial Fluid for Diagnosis of Orthopedic Infections

High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defensins in Synovial Fluid for Diagnosis of Orthopedic Infections

Detection of α‐defensin in synovial fluids by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry as an innovative and cost‐effective assay for improved definition of periprosthetic joint infections

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

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