Evaluation of myeloperoxidase in synovial fluid as a biomarker for chronic periprosthetic joint infection

Ikeda, Shinsuke; Uchiyama, Katsufumi; Minegishi, Yojiro; Nakamura, Masaki; Takaso, Masashi

doi:10.1007/s00264-020-04753-0

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…9-11 In the joint cavity, synovial fluid (SF) can provide nutrition and lubrication to the articular cartilage, which may accumulate in a pathologic joint, reflecting the ongoing process of some disorders. 12 There was a study showing the greater SF adiponectin/leptin ratio was associated with less pain of patients with knee OA. 13…”

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis

Zhang

Dai

et al. 2021

CARTILAGE

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Objectives The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. Materials and Methods The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. Results No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels ( P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores ( P < 0.05), which were still significant after adjusting for confounding factors ( P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA ( P < 0.001). Conclusion SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

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Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis

Zhang

Dai

et al. 2021

CARTILAGE

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“…Myeloperoxidase (MPO) is a bactericidal enzyme that acts against pathogenic microorganisms, such as in PJI. In a small cohort study of 37 patients, MPO levels were significantly higher in the chronic PJI group than in the aseptic failure group (p < 0.001) (p < 0.001) ( Ikeda et al., 2020 ) ( Table 5 ). Another marker is cell-free deoxyribonucleic acid (cf-DNA) in synovial fluid and peripheral blood ( Echeverria et al., 2021 ; Cobra et al., 2022 ).…”

Section: Resultsmentioning

confidence: 97%

Novel diagnostic markers for periprosthetic joint infection: a systematic review

Schindler

Walter

Maderbacher

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundIdentifying novel biomarkers that are both specific and sensitive to periprosthetic joint infection (PJI) has the potential to improve diagnostic accuracy and ultimately enhance patient outcomes. Therefore, the aim of this systematic review is to identify and evaluate the effectiveness of novel biomarkers for the diagnosis of PJI.MethodsWe searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases from January 1, 2018, to September 30, 2022, using the search terms “periprosthetic joint infection,” “prosthetic joint infection,” or “periprosthetic infection” as the diagnosis of interest and the target index, combined with the term “marker.” We excluded articles that mentioned established biomarkers such as CRP, ESR, Interleukin 6, Alpha defensin, PCT (procalcitonin), and LC (leucocyte cell count). We used the MSIS, ICM, or EBJS criteria for PJI as the reference standard during quality assessment.ResultsWe collected 19 studies that analyzed fourteen different novel biomarkers. Proteins were the most commonly analyzed biomarkers (nine studies), followed by molecules (three studies), exosomes (two studies), DNA (two studies), interleukins (one study), and lysosomes (one study). Calprotectin was a frequently analyzed and promising marker. In the scenario where the threshold was set at ≥50-mg/mL, the calprotectin point-of-care (POC) performance showed a high sensitivity of 98.1% and a specificity of 95.7%.ConclusionNone of the analyzed biomarkers demonstrated outstanding performance compared to the established parameters used for standardized treatment based on established PJI definitions. Further studies are needed to determine the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings.

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“…We found that three NET-related biomarkers, cf-DNA, H3Cit, and MPO, are increased in the synovial fluid of patients who have PJI. Previous studies have shown that there were higher levels of cf-DNA [4] and MPO [7] in the synovial fluid of patients with PJI. Such studies have identified the NETosis process as a potential source of both biomarkers; however, the occurrence of this process in PJI has not been addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Other putative biomarkers for NETs are cell-free DNA (cf-DNA) and granule enzymes such as myeloperoxidase (MPO), which may have sources other than NET formation, such as cell death and degranulation [13,17]. Recently, cf-DNA [4] and MPO [7] have been shown to be increased in the synovial fluid of patients with chronic PJI. However, little is known about the NET release process (because of NETosis) in PJI.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections

de Sandes Kimura,

Mozella,

Cobra

et al. 2023

Clin Orthop Relat Res

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Background The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. Questions/purposes (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell‐free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? Methods Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. Results Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. Conclusion Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. Level of Evidence Level II, diagnostic study.

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Evaluation of myeloperoxidase in synovial fluid as a biomarker for chronic periprosthetic joint infection

Cited by 11 publications

References 27 publications

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis

Novel diagnostic markers for periprosthetic joint infection: a systematic review

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections

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