LTF, PRTN3, and MNDA in Synovial Fluid As Promising Biomarkers for Periprosthetic Joint Infection: Identification by Quadrupole Orbital-Trap Mass Spectrometry

Background: Diagnosing periprosthetic joint infection (PJI) requires various laboratory and clinical criteria. The purpose of this study was to explore novel biomarkers that could rapidly diagnose PJI with high accuracy.

Methods: In this retrospective study of prospectively collected samples, 50 synovial fluid aspirates, 20 from the hip and 30 from the knee, were collected before surgery; 25 of the patients were diagnosed as having aseptic loosening (non-PJI) and 25, as having PJI according to the Musculoskeletal Infection Society criteria. A quadrupole orbital-trap mass spectrometry (MS) instrument was used to compare expression of proteins in patients with and without PJI. Proteins that were most efficacious for diagnosis of PJI were then determined using prediction analysis of microarray software and a random forest model. The most promising proteins were selected, and altered expression of these selected proteins was verified by ELISA (enzyme-linked immunosorbent assay) in an extended sample cohort.

Results: A total of 256 proteins were significantly upregulated (≥3.0-fold) and 14 proteins were downregulated in synovial fluid of patients with PJI compared with patients without PJI. The 3 most promising proteins were lactoferrin (LTF), polymorphonuclear leukocyte serine protease 3 (PRTN3), and myeloid nuclear differentiation antigen (MNDA). When MS was used for diagnosis of PJI, the area under the curve was 0.9888 for LTF, 0.9488 for PRTN3, and 0.9632 for MNDA. ELISA results verified that LTF, MNDA, and PRTN3 were sensitive, while LTF and MNDA were specific, for diagnosis of PJI.

Conclusions: This proteomic study identified a previously noted protein and 2 novel candidate proteins as promising synovial fluid biomarkers for PJI diagnosis, and they should be further validated in future clinical trials.

Level Of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.