Joshua Parry1, Jiho Hwang1, Cedric F Stahel1, Corey Henderson1,2, Jason Nadeau1, Stephen Stacey1, Kathryn Beauchamp3, Ernest E Moore3, Philip F Stahel4,5. 1. Department of Orthopaedics, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA. 2. Rocky Vista University, College of Osteopathic Medicine, Parker, CO, 80134, USA. 3. Department of Surgery, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA. 4. Department of Orthopaedics, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA. Philip.Stahel@gmail.com. 5. Rocky Vista University, College of Osteopathic Medicine, Parker, CO, 80134, USA. Philip.Stahel@gmail.com.
Abstract
PURPOSE: Terminal complement pathway activation after traumatic brain injury (TBI) leads to formation of the membrane attack complex (MAC/C5b-9) which induces neuronal cell death and host-mediated secondary brain injury. Serum levels of soluble MAC (sC5b-9) have not been previously determined in patients with isolated TBI. METHODS: A prospective observational cohort study was performed during a 5-year time-period on adult patients with isolated TBI admitted to an academic level I trauma center in the United States. Controls consisted of patients with femur shaft fractures with or without TBI to mitigate the effect of systemic complement activation by peripheral trauma. Healthy volunteers served as internal controls. The sC5b-9 serum concentrations were measured on the day of admission by enzyme-linked immunosorbent assay (ELISA) and compared between the study cohorts. Univariate analysis was performed to determine independent predictive variables of major complications during hospital admission. RESULTS: Serum sC5b-9 levels were significantly elevated in patients with isolated TBI (n = 42), compared to patients with isolated femoral shaft fractures (n = 36) or combined TBI and femoral shaft fractures (n = 30; p < 0.05). There was no significant difference in serum sC5b-9 levels between the femur group and the combined injury group, compared to the healthy volunteers (n = 21). Univariate analysis revealed serum sC5b-9 levels as an independent predictor of major postinjury complications after isolated TBI (p < 0.01). CONCLUSION: The soluble terminal complement complex sC5b-9 represents a potential novel serum biomarker specific for isolated head injuries, since peripheral trauma did not appear to affect the serum sC5b-9 levels.
PURPOSE: Terminal complement pathway activation after traumatic brain injury (TBI) leads to formation of the membrane attack complex (MAC/C5b-9) which induces neuronal cell death and host-mediated secondary brain injury. Serum levels of soluble MAC (sC5b-9) have not been previously determined in patients with isolated TBI. METHODS: A prospective observational cohort study was performed during a 5-year time-period on adult patients with isolated TBI admitted to an academic level I trauma center in the United States. Controls consisted of patients with femur shaft fractures with or without TBI to mitigate the effect of systemic complement activation by peripheral trauma. Healthy volunteers served as internal controls. The sC5b-9 serum concentrations were measured on the day of admission by enzyme-linked immunosorbent assay (ELISA) and compared between the study cohorts. Univariate analysis was performed to determine independent predictive variables of major complications during hospital admission. RESULTS: Serum sC5b-9 levels were significantly elevated in patients with isolated TBI (n = 42), compared to patients with isolated femoral shaft fractures (n = 36) or combined TBI and femoral shaft fractures (n = 30; p < 0.05). There was no significant difference in serum sC5b-9 levels between the femur group and the combined injury group, compared to the healthy volunteers (n = 21). Univariate analysis revealed serum sC5b-9 levels as an independent predictor of major postinjury complications after isolated TBI (p < 0.01). CONCLUSION: The soluble terminal complement complex sC5b-9 represents a potential novel serum biomarker specific for isolated head injuries, since peripheral trauma did not appear to affect the serum sC5b-9 levels.
Authors: Inge A M van Erp; Thomas A van Essen; Kees Fluiter; Erik van Zwet; Peter van Vliet; Frank Baas; Iain Haitsma; Dagmar Verbaan; Bert Coert; Godard C W de Ruiter; Wouter A Moojen; Mathieu van der Jagt; Wilco C Peul Journal: Trials Date: 2021-12-04 Impact factor: 2.279