Proteomic Analyses of Plasma from Patients with Fracture Related Infection Reveals Systemic Activation of the Complement and Coagulation Cascades

Abstract

OBJECTIVES: To compare plasma proteomes of patients with confirmed fracture related infections (FRIs) matched to noninfected controls using liquid chromatography-mass spectrometry (LC-MS) METHODS: Design: Prospective Case-Control Study Setting: Single, Academic, Level 1 Trauma Center Patient Selection Criteria: Patients meeting confirmatory FRI criteria were matched to controls without infection based on fracture region, age, and time after surgery from June 2019 to January 2022. Tandem Mass Tag LC-MS analysis of patient plasma samples was performed. Outcome Measures and Comparisons: Protein abundance ratios in plasma for FRI patients compared to matched controls without infection were calculated. RESULTS: Twenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls . Abundance ratios for over 1,000 proteins were measured in the 54 plasma samples. Seventy-three proteins were found to be increased or decreased in FRI patients compared to the matched controls (unadjusted t-test p<0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component (PC) analysis (PCA) to reduce the dimensionality of the large proteomics data set. A three component PCA accounted for 45.7% of the variation in the data set and had 88.9% specificity for the diagnosis of FRI. STRING protein-protein interaction network analysis of these three PCs revealed activation of the complement and coagulation cascades via the Reactome pathway database (false discovery rates<0.05). CONCLUSIONS: Proteomic analyses of plasma from FRI patients demonstrates systemic activation of the complement and coagulation cascades. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics.