Characterization of the Complement Cascade in Human Traumatic Brain Injury

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Neuroinflammation, driven by complement activation, worsens outcomes in severe traumatic brain injury (TBI).
• Previous studies on complement in TBI were limited to animal models and post-mortem tissues.
• Characterizing the complement cascade in a substantial human TBI cohort is crucial.

Purpose of the Study:

• To investigate the complement cascade, focusing on lectin pathway initiators, in TBI patients versus healthy controls.
• To analyze temporal profiles of complement proteins post-TBI.
• To assess the association between complement proteins and clinical outcomes in TBI.

Main Methods:

• Plasma samples from 64 TBI patients (days 1-7, 42, 365) and 17 controls were analyzed for 10 complement proteins.
• Proteins included initiators (MBL, MASP2, ficolin3), effectors (C4b, C2, factor D, factor I), and downstream components (C5, C5a, C5b9).
• Assays used were single and multiplexing protein assays; clinical data included injury severity and Glasgow Outcome Scale Extended.

Main Results:

• Seven of ten complement proteins differed significantly between TBI patients and controls (p < 0.05).
• Ficolin3 was significantly lower in TBI patients, persisting even one year post-injury (p < 0.001).
• Elevated C4b, C5, and factor I were associated with unfavorable outcomes; C5 showed a robust independent prognostic value (OR: 1.53, p < 0.001).

Conclusions:

• The study characterized the complement cascade in human TBI with high temporal resolution.
• Complement component C5 is a significant independent predictor of unfavorable outcome 6 months post-TBI.
• Targeting the complement system presents a potential therapeutic avenue for TBI management.