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Updated: Dec 20, 2025

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?
Joshua Parry1, Jiho Hwang1, Cedric F Stahel1
1Department of Orthopaedics, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA.
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.
Insights
Elevated serum levels of soluble membrane attack complex (sC5b-9) indicate traumatic brain injury (TBI). This biomarker predicts major complications following isolated TBI, suggesting its potential for diagnosing head injuries.
Area of Science:
- Neuroscience
- Immunology
- Trauma Research
Background:
- Traumatic brain injury (TBI) activates the terminal complement pathway, forming the membrane attack complex (MAC/C5b-9).
- MAC formation contributes to neuronal death and secondary brain injury.
- Serum levels of soluble MAC (sC5b-9) in isolated TBI patients remain undetermined.
Purpose of the Study:
- To determine serum sC5b-9 levels in patients with isolated TBI.
- To investigate sC5b-9 as a potential biomarker for isolated TBI.
- To assess the relationship between sC5b-9 levels and post-TBI complications.
Main Methods:
- Prospective observational cohort study of adult isolated TBI patients.
- Control groups included femur fracture patients and healthy volunteers.
- Serum sC5b-9 concentrations measured via ELISA on admission.
- Univariate analysis to identify predictors of hospital complications.
Main Results:
- Serum sC5b-9 levels were significantly higher in isolated TBI patients compared to femur fracture patients.
- No significant difference in sC5b-9 levels between femur fracture/combined injury groups and healthy volunteers.
- Elevated serum sC5b-9 independently predicted major post-TBI complications.
Conclusions:
- Soluble C5b-9 (sC5b-9) may serve as a novel serum biomarker specific to isolated head injuries.
- Peripheral trauma does not appear to significantly influence serum sC5b-9 levels.
- sC5b-9 shows potential for diagnosing TBI and predicting patient outcomes.
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