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Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?

  • Original Article
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European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

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.

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Abbreviations

COMIRB:

Colorado Multiple Institutional Review Board

ELISA:

Enzyme-linked immunosorbent assay

GCS:

Glasgow Coma Scale

ICU:

Intensive care unit

ISS:

Injury Severity Score

MAC:

Membrane attack complex

OTA:

Orthopaedic Trauma Association

sC5b-9:

Soluble terminal complement complex C5b-9

SD:

Standard deviation

TBI:

Traumatic brain injury

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Acknowledgements

This study was supported by a peer-reviewed industrial grant to the senior author (P.F.S.) by Stryker Corporation, Kalamazoo, MI (USA).

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA

    Joshua Parry, Jiho Hwang, Cedric F. Stahel, Corey Henderson, Jason Nadeau, Stephen Stacey & Philip F. Stahel

  2. Rocky Vista University, College of Osteopathic Medicine, Parker, CO, 80134, USA

    Corey Henderson & Philip F. Stahel

  3. Department of Surgery, Denver Health Medical Center and University of Colorado School of Medicine, Denver, CO, 80204, USA

    Kathryn Beauchamp & Ernest E. Moore

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  1. Joshua Parry
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Contributions

JP and JH contributed to clinical data analysis and drafting of the manuscript. CFS and CH performed the sC5b-9 ELISA experiments and analysis of the complement data. JN and SS contributed to interpretation of the data and drafting of the manuscript. KB, EEM, and PFS designed the study, supervised the experiments, and contributed to interpretation of the data and drafting of the manuscript. PFS provided the first draft of the original manuscript. All authors read and approved the final manuscript prior to submission.

Corresponding author

Correspondence to Philip F. Stahel.

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Conflict of interest

P.F.S. is the recipient of a peer-reviewed research grant by Stryker Corporation (Kalamazoo, MI) for this project, and the co-inventor of a United States patent No. 11,441,828 entitled: “Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury, and related conditions.” The other authors declare no conflict of interest related to this project.

Ethics approval, consent for participation and publication

The study protocol was approved by the Colorado Multiple Institutional Review Board (COMIRB) #10-0638. The IRB protocol allowed a waiver of consent due to minimal risk.

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Parry, J., Hwang, J., Stahel, C.F. et al. Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?. Eur J Trauma Emerg Surg 47, 1491–1497 (2021). https://doi.org/10.1007/s00068-020-01407-z

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