Synovial fluid neutrophil extracellular traps could improve the diagnosis of periprosthetic joint infection

Abstract

Aims This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120.

Active myeloperoxidase: a promising biomarker to differentiate “acute” and “low-grade” peri-prosthetic joint infections from aseptic failures

“…Recent research has shown that their involvement in the pathogenesis of PJI could take place through the formation of neutrophil extracellular traps (NETosis) ( Cai et al, 2023 ). NETosis reflects part of the innate immune response to pathogens.…”

Prosthetic spacers in two-stage revision for knee periprosthetic joint infection achieve better function and similar infection control

“… 26 In terms of pathogen diagnosis, similar results were obtained in this study. Currently, with the development of metagenomic next-generation sequencing (mNGS), broad-range polymerase chain reaction (BR-PCR), and other molecular diagnostic methods, 27 , 28 the molecular detection results could be used as a supplement for the diagnosis of PJI in addition to microbial culture. We achieved good clinical outcomes through standardized revision procedures, which indicated that, regardless of the kind of spacer, standardized treatment for pathogenic bacteria, including multiple specimen collection procedures, thorough debridement, and the combined topical and systemic application of antibiotics, 29 is the key to long-term infection management.…”

Periprosthetic joint infection and immunity: Current understanding of host–microbe interplay

“…[87][88][89][90] Use of neutrophil extracellular traps (NETs) as a synovial fluid biomarker has shown usefulness at effectively diagnosing PJI in culture-negative PJI, fungal PJI, and those on antibiotics with an area under the curve (AUC) between 0.95 and 0.99. 91 Calprotectin, a protein found in the cytoplasm of neutrophils, has high sensitivity and high specificity and may be useful as a ruleout test for PJI. 92 Cytokines and chemokines including chemokine (C-C motif) ligand 20 (CCL20), cytokine/chemokine regulator oncostatin M (OSM), a danger-associated molecular pattern known as extracellular newly identified receptor for advanced glycation endproducts binding protein (EN-RAGE), IL-8, and IL-6 are increased in sonicate fluid samples compared with aseptic revisions and are not differentially expressed based on infective species.…”

“…LE is an enzyme that is produced by activated neutrophils that can be detected by a colorimetric strip test and α‐defensin, an antimicrobial peptide secreted by neutrophils, can be detected by enzyme‐linked immunosorbent assay (ELISA) both with high sensitivity and specificity 87–90 . Use of neutrophil extracellular traps (NETs) as a synovial fluid biomarker has shown usefulness at effectively diagnosing PJI in culture‐negative PJI, fungal PJI, and those on antibiotics with an area under the curve (AUC) between 0.95 and 0.99 91 . Calprotectin, a protein found in the cytoplasm of neutrophils, has high sensitivity and high specificity and may be useful as a rule‐out test for PJI 92 …”