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Elevated Serum Complement C1q Levels After Traumatic Brain Injury [Letter]

Authors Paiva WS , Ortiz J, Amorim RL 

Received 12 April 2022

Accepted for publication 21 April 2022

Published 4 May 2022 Volume 2022:18 Pages 951—952


Checked for plagiarism Yes

Editor who approved publication: Dr Yuping Ning

Wellingson Silva Paiva,1,2 Josimar Ortiz,1 Robson Luis Amorim2

1Division of Neurosurgery, Department of Neurology, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil; 2LIM 62, Laboratory of Medical Investigation in Neurosurgery, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil

Correspondence: Wellingson Silva Paiva, Division of Neurosurgery, Hospital das Clinicas da FMUSP, 255 Dr Eneas Aguiar Ave, São Paulo, 05203000, Brazil, Tel +55 11 25486900, Fax +55 11 25486909, Email [email protected]

View the original paper by Dr Yan and colleagues

Dear Editor

We have read with great interest the recent paper by Yan et al,1 published in Neuropsychiatric Disease and Treatment, discussing complement elements and prognosis in traumatic brain injury (TBI). Trauma is the leading cause of death in people aged 1–44 years. TBI is the main determinant of morbidity, disability, and mortality within this group.2 Severe TBI is associated with a mortality rate of 30–70%,2 and recovery in survivors is marked by severe neurological sequelae and a very impaired quality of life.3 TBI translates into neuronal cell death, brain edema, and blood–brain barrier disruption, through primary and secondary injuries. An intense systemic inflammatory response, affecting both traumatized and healthy brain tissue, is frequent in TBI.4 The inflammatory stress response includes complement activation and up-regulation of adhesion molecules on the endothelium of brain vessels associated with neutrophil accumulation and cytokine production.5 However, the real prognostic value of the complement system in patients with TBI is not well defined.6

The complement system consists of an enzyme “cascade” that helps defend against infections. Many proteins of the complement system occur in serum as inactive enzyme precursors (zymogens); others are found on cell surfaces.4,6,7 The C1q complement system seems to be an important element in secondary brain injury.1

In the article by Yan et al,1 they describe the relationship between serum complement C1q levels and the severity of TBI and prognosis after TBI. This is a prospective study with a 6-month outcome analysis. It is especially exciting to have a new prognostic factor for patients with severe TBI. Serum C1q has an inversely proportional relationship with Glasgow Coma Scale (GCS) and Extended Glasgow Outcome Scale (GOSE) scores, configuring the complement system as a prognostic predictor and starting point from which to develop new therapeutic approaches.

However, despite the multivariate analysis, some important facts were not included.

Based on the analysis of this paper, we have highlighted three important points to be discussed:

Seventy-nine patients had abnormal cisterns and another 75 had a midline displacement greater than 5 mm, indicating critical cases of TBI. However, 87 had an epidural hematoma, which usually has a good prognosis, and this proportion of epidural hematomas appears to be very high compared to a level 1 trauma center.

A second point concerns the best time to collect blood for complement system analysis. In the published sample, the time of collection varied considerably. Perhaps a standardization of the time of blood collection could result in more accurate data on the prognostic role of C1q in TBI.

A third aspect is about the acute subdural hematoma that was reported in 111 patients; however, there was no mention of surgical treatment, generating a question about surgical or conservative management, a fact that affects the final outcome and prognosis. Important information, such as injuries associated with TBI, will have an impact on management and may facilitate the understanding of the true role of C1q complement in neuroinflammation. These small caveats, however, do not take away the main relevant messages and discussion raised by Yan et al.


The authors report no conflicts of interest in this communication.


1. Yan XJ, Li YB, Liu W, Wu HY, Yu GF. Elevated Serum Complement C1q Levels After Traumatic Brain Injury and Its Association with Poor Prognosis. Neuropsychiatr Dis Treat. 2022;18:47–55. doi:10.2147/NDT.S348682.

2. Andrade AF, Paiva WS, Amorim RL, Figueiredo EG, Rusafa Neto E, Teixeira MJ. Mecanismos de lesão cerebral no traumatismo cranioencefálico [The pathophysiological mechanisms following traumatic brain injury]. Rev Assoc Med Bras. 2009;55(1):75–81.

3. Neville IS, Hayashi CY, El Hajj SA, et al. Repetitive Transcranial Magnetic Stimulation (rTMS) for the cognitive rehabilitation of traumatic brain injury (TBI) victims: study protocol for a randomized controlled trial. Trials. 2015;16:440. doi:10.1186/s13063-015-0944-2.

4. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015;2(3):258–270. doi:10.1016/S2215-0366(14)00122-9

5. Hammad A, Westacott L, Zaben M. The role of the complement system in traumatic brain injury: a review. J Neuroinflammation. 2018;15(1):24. doi:10.1186/s12974-018-1066-z.

6. Gopcevic A, Mazul-Sunko B, Marout J, et al. Plasma interleukin-8 as a potential predictor of mortality in adult patients with severe traumatic brain injury. Tohoku J Exp Med. 2007;211(4):387–393.

7. Holste K, Xia F, Garton HJ, et al. The role of complement in brain injury following intracerebral hemorrhage: a review. Exp Neurol. 2021;340:113654.

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