Introduction
The incidence of total knee and hip arthroplasty (TKA and THA) isrising due to demographic changes, leading to an increase in postoperative complications like prosthetic joint infection (PJI), aseptic failure, and chronic pain. The diagnosis of PJI is complicated and lacks a gold standard. Additionally, the diagnosis of chronic joint pain, which does not require revision surgery, is difficult to distinguish from PJI and aseptic loosening.

Methods
This study utilized blood plasma samples from the Prosthetic-Related-Infection and Pain (PRIS) study. Patients (N=98) were separated into several disease and outcome groups and samples were taken at up to four timepoints from baseline to follow-ups. Plasma samples were analyzed by utilizing quantitative label-free liquid chromatography–mass spectrometry. The statistical analysis was conducted in Perseus and Stata. Bioinformatic analyses were explored using the STRING database.

Results
The deep proteome analysis of the serum samples revealed more than 650 quantifiable proteins, of which multiple proteins were associated with clinical outcome measures like pain. A comprehensive analysis of the regulated proteins by, e.g., STRING network analysis of protein–protein interactions revealed that chronic joint pain is associated with pathways in coagulation, cholesterol metabolism and actin filament-based processes. Further, PJI and aseptic loosening were associated with pathways of the extracellular matrix. Subsequently, volcano plots identified significantly upregulated expression of seven proteins (Protein s100-A8/9, C-reactive protein, Serum amyloid A-1/2, Histone H2A type 1-H, and Von Wildebrand factor) in the PJI group and four proteins (Kallistatin, Haemoglobin subunit beta, 4-Aminobutyrate aminotransferase, mitochondrial, and Phosphatidylinositol-glycan-specific phospholipase D) in the chronic pain group.

Conclusion
The comprehensive panel of biomarkers identified in this study could possibly aid in the diagnosis of PJI and chronic joint pain following TKA or THA. Subsets of proteins allowed separation of the patient groups. These findings have the potential of enhancing patient outcomes and quality of life.