Synovial fluid proteomic biomarkers in periprosthetic joint infection: A systematic review with gene ontology and protein network analyses.
systematic_review · Level I
Where this comes from
- Record sourced from PubMed, PMID 42519810.
- Also identified by DOI 10.1002/jeo2.70853 and PMC identifier 13384346.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty associated with significant morbidity, implant failure and increased healthcare costs. Diagnosis remains challenging, particularly in low-grade and culture-negative infections, because conventional markers lack specificity. Proteomic analyses may identify more reliable synovial biomarkers and provide insights into the molecular mechanisms underlying PJI. A systematic review was conducted according to PRISMA guidelines using PubMed and Scopus databases. Studies published within the last 10 years involving adults undergoing revision hip or knee arthroplasty for suspected PJI and assessing synovial fluid biomarkers by proteomic or immunoassay techniques (liquid chromatography-tandem mass spectrometry, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, enzyme-linked immunosorbent assay) were included. Functional enrichment analyses (gene ontology [GO], Kyoto encyclopaedia of genes and genomes [KEGG], human phenotype ontology [HPO], DISEASES and protein-protein interaction (PPI) network analyses were performed. Six studies met the inclusion criteria. A focused set of dysregulated synovial proteins was identified, predominantly related to innate immunity and inflammation, including lactoferrin, myeloperoxidase, lysozyme C, PRTN3, defensin alpha 1, defensin alpha 3, calprotectin (S100 calcium-binding proteins A8 and A9), annexin A6, alpha-2-HS-glycoprotein (Fetuin-A), MNDA, GRO-α, interleukin (IL)-8 and IL-5. GO and KEGG analyses demonstrated enrichment of antimicrobial defense and cytokine-mediated inflammatory pathways. PPI analysis identified key hub proteins involved in inflammatory and oxidative stress responses, while HPO and DISEASES analyses further supported their association with immune dysregulation and infectious inflammatory conditions. Synovial proteomic and immuno-inflammatory biomarkers may improve diagnostic accuracy in PJI, particularly in low-grade and culture-negative infections. Biomarker panels including α-defensins and calprotectin (S100A8/A9) represent promising next-generation diagnostic tools. Further multicenter studies are needed to validate these findings and facilitate their integration into standardised diagnostic algorithms. Levels II-III.