Evaluation of Serum NLRC4 as a Potential Prognostic Biochemical Marker in Humans with Severe Traumatic Brain Injury: A Prospective Cohort Study

Objective: Involvement of NLR CARD domain containing 4 (NLRC4) in neuroinflammation has been demonstrated. The aim of this study was to ascertain the prognostic role of serum NLRC4 in severe traumatic brain injury (sTBI).Methods: In this prospective cohort study including 140 sTBI patients and 140 controls, serum NLRC4 levels were quantified. Follow-up time was 180 days after trauma and poor prognosis was designated as extended Glasgow outcome scale (GOSE) scores of 1-4. Severity correlations and prognosis associations were determined under multivariate models.Results: Enhanced serum NLRC4 levels after sTBI, in comparison to controls (median, 0.8 ng/mL versus 0.1 ng/mL; P < 0.001), were independently correlated with Glasgow coma scale (GCS) scores (13, -0.091; 95% confidence interval (CI), -0.161-0.021; P = 0.011), Rotterdam computed tomography (CT) scores (13, 0.136; 95% CI, 0.024-0.248; P = 0.018), serum C-reactive protein levels (13, 0.016; 95% CI, 0.002-0.030; P = 0.025) and 180-day GOSE scores (13, -0.906; 95% CI, -1.632-0.180; P = 0.015); and were independently predictive of 180-day death (odds ratio, 4.307; 95% CI, 1.706-10.879; P = 0.014)), overall survival (hazard ratio, 2.360; 95% CI, 1.118-4.981; P = 0.040) and poor prognosis (odds ratio, 6.705; 95% CI, 2.889-15.561; P = 0.016). Under receiver operating characteristic curve, combination of serum NLRC4 levels, GCS scores and Rotterdam CT scores had significantly higher death predictive ability than Rotterdam CT scores (P = 0.040), but not than GCS scores (P = 0.070); and exhibited substantially higher predictive capability for poor prognosis than Rotterdam CT scores (P < 0.001) and GCS scores alone (P = 0.023). Conclusion: There is a dramatical elevation of serum NLRC4 levels after sTBI, which has strong correlation with severity and inflammation, and is significantly associated with long-term death and poor outcome, substantializing serum NLRC4 as an inflam-matory, prognostic biomarker in sTBI.