Calprotectin identified as a key differentially expressed plasma biomarker in periprosthetic joint infection against aseptic failure: a precision health proteomics study.

BACKGROUND: Periprosthetic joint infection (PJI) is a debilitating and dangerous complication following joint arthroplasty procedures. With the increasing incidence of arthroplasty procedures, the burden of PJI is expected to continually grow. A correct and early diagnosis of PJI proves difficult, with the lack of a single standardized molecular test. The utilization of serology-based biomarkers would provide a non-invasive sampling method; however, these methods have not proven sufficient to satisfy the diagnostic criteria. METHODS: The present study aimed to employ liquid chromatography/mass spectrometry-based (LC-MS) techniques to explore the proteomic profile of plasma samples derived from a prospective Danish PJI cohort, PRIS, to identify relevant proteins that are significantly differentially expressed in acute PJI compared to those with aseptic failure or chronic pain related to the prosthesis. Serum from patients included in the LC-MS analysis was measured for a biomarker of neutrophil activity, CPa9-HNE, measuring a neo-epitope of neutrophil elastase-cleaved calprotectin. RESULTS: A total of 656 plasma proteins were quantified by the discovery proteomic approach, and differential abundance analysis showed increased abundance of calprotectin heterodimers, S100A8, and S100A9 in acute PJI samples compared to both aseptic failure and chronic pain. Functional enrichment of the significantly regulated proteins in acute PJI, compared to aseptic failure and chronic pain, showed an upregulation of acute immune-related pathways. Serum levels of a biomarker of neutrophil activity, an elastase-derived calprotectin neo-epitope, CPa9-HNE, showed statistically significant differences between infection and both aseptic failure and chronic pain in the same cohort, supporting the findings in LC-MS analysis. CONCLUSION: Plasma LC-MS proteomics and targeted measurement of CPa9-HNE neutrophil activity biomarker in matched serum samples of patients with PJI, aseptic failure, and chronic pain show significant upregulation of calprotectin heterodimers, S100A8 and S100A9, as well as CPa9-HNE in patients with PJI.