343 Diagnostic and Prognostic Utility of Inflammatory Cytokines and Acute Phase Proteins in Traumatic Brain Injury: Results From the 18-Center TRACK-TBI Study

INTRODUCTION: Systemic and neuroinflammatory responses mediate secondary injuries after traumatic brain injury (TBI), which lead to adverse outcomes. Identifying biomarkers of secondary injury may enable early recognition of patients at risk of clinical decline and delineate targets for therapeutic modulation. METHODS: The 18-center TRACK-TBI Study (years 2014-2018) enrolled patients who received head CT within 24-hours of TBI. In 394 TBI patients, 100 orthopedic trauma controls (OCs), and 67 healthy controls (HCs) with plasma biomarkers within 24-hours (MesoScale Diagnostics) and 6-month outcome, biomarker levels were compared between CT-positive/CT-negative TBI, Glasgow Coma Scale (GCS)=3-12/13-15, and unfavorable/favorable outcome (Glasgow Outcome Sale-Extended=1-4/5-8). Differences between medians (fold-change) and discrimination (AUC) were reported. Significance threshold p<0.002 (0.05÷26 biomarkers). Comparisons reported at p<0.0001(*) unless denoted. RESULTS: Eleven biomarkers differentiated TBI/HC, TBI/OC, TBI severity, and 6-month outcome. Fold-changes and AUCs were consistent across severity comparisons (CT+/CT-, GCS=3-12/13-15, respectively): interleukin-10 (IL-10; 6.4-fold*/7.6-fold*; AUC=0.81/0.89), IL-6 (4.6*/3.7*; AUC=0.82/0.87), IL-2 (3.3*/4.1*; AUC=0.82/0.85), tumor necrosis factor-alpha (TNFa; 2.3*/3.0*; AUC=0.81/0.85), IL-15 (1.4*/1.5*; AUC=0.77/0.85), c-reactive protein (CRP; 8.8*/10.2*; AUC=0.79/0.81), serum amyloid A (SAA; 19.8*/18.6*; AUC=0.78/0.0.80), IL-1b (3.4*/4.3*; AUC=0.76/0.83), IL-4 (3.4*/3.9*; AUC=0.74/0.79), IL-17a (1.7*/2.0*; AUC=0.69/0.74), IL-12p70 (1.4*/1.6*; AUC=0.65/0.70). Fold-changes and AUCs were consistent for unfavorable outcome: IL-10 (5.6-fold*/AUC=0.83), IL-6 (1.5*/AUC=0.75), IL-2 (3.9*/AUC=0.81), TNFa (2.8*/AUC=0.77), IL-15 (1.6*/AUC=0.79), CRP (4.9*/AUC=0.71), SAA (4.1*/AUC=0.67), IL-1b (2.7*/AUC=0.74), IL-4 (2.5*/AUC=0.73), IL-17a (2.1*/AUC=0.73), IL-12p70 (1.7*/AUC=0.70). Bivariate correlations (Spearman’s ρ>0.7) emerged amongst IL-1b, IL-2, IL-4, TNFa (with several other markers), and between CRP/SAA. CONCLUSIONS: We identified 11 blood-based inflammatory proteins with diagnostic and prognostic relevance (CRP, SAA, IL-1b, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-15, IL-17a, TNFa). These biomarkers distinguished TBI severity and 6-month unfavorable outcome with consistent magnitudes of association.