Elsevier

Clinica Chimica Acta

Volume 520, September 2021, Pages 101-107
Clinica Chimica Acta

Serum calprotectin as a prognostic predictor in severe traumatic brain injury

https://doi.org/10.1016/j.cca.2021.06.009Get rights and content

Highlights

  • Serum calprotectin emerges as an independent prognostic predictor at 90 days after sTBI.

  • Serum calprotectin levels in sTBI patients have high prognostic predictive capability.

  • Serum calprotectin levels are closely related to inflammatory reaction after sTBI.

Abstract

Background

Calprotectin plays an important role during inflammation. We intended to explore the prognostic value of serum calprotectin levels in patients with severe traumatic brain injury (sTBI).

Methods

In this prospective cohort study of 149 sTBI patients, we determined the relationship between serum calprotectin levels and 90-day overall survival plus poor outcome (Glasgow outcome scale score of 1–3) after sTBI, and analyzed its associations with Rotterdam computerized tomography (CT) scores, Glasgow coma scale (GCS) scores and two markers of inflammatory reaction including serum C-reactive protein levels and blood leucocyte count.

Results

Serum calprotectin levels were significantly correlated with Rotterdam CT scores, GCS scores, serum C-reactive protein levels and blood leucocyte count. Patients with poor outcome at 90 days displayed higher serum calprotectin levels than the other remainders. Serum calprotectin appeared as an independent predictor for 90-day overall survival and poor outcome. Under receiver operating characteristic curve, serum calprotectin levels exhibited an efficient discrimination capacity for 90-day poor outcome.

Conclusions

Serum calprotectin levels are significantly correlated with inflammation, trauma severity and poor outcome at 90 days in sTBI patients, suggesting that serum calprotectin may be a biomarker for providing complementary prognostic information to identify patients at risk of poor outcome after sTBI.

Introduction

Severe traumatic brain injury (sTBI) is one of the most frequent causes of permanent disability in adults [1]. Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification are the two important systems for assessing trauma severity and predicting prognosis after head trauma [2], [3]. Even after years of research, pathophysiology of secondary brain injury following brain trauma is not yet fully understood [4]. Inflammation is increasingly recognized as a key element in the pathological progression of brain trauma [5]. External force causes an immediate local immuno-inflammatory reaction with strong activation of microglia, astrocytes and endothelial cells, and rapid release of cytokines both from activated cells and endothelium [6]. This non-specific response after brain injury leads to damaged blood–brain barrier permeability and infiltration of inflammatory cells into the injured brain area, which subsequently increases tissue injury [7]. Thus, some inflammatory molecules have been reported as predictive markers of severity and outcome in sTBI [8].

Calprotectin (S100A8/A9), also named myeloid related protein 8/14, is a stable heteromorphic dimer complex of S100A8 and S100A9 [9]. Calprotectin participates in the inflammatory cascade and has a wide range of proinflammatory functions, including aggregation of leukocytes, promotion of cytokine, chemokine production, and the regulation of leukocyte adhesion and migration [10]. Reportedly, calprotectin levels in peripheral blood, in close correlation with traditional markers of oxidative stress and inflammation, were independently associated with mortality, functional dependence and hemorrhagic transformation in acute ischemic stroke [11], [12], [13]. Also, in patients with aneurysmal subarachnoid hemorrhage, serum calprotectin levels were significantly correlated with the clinical severity and the poor prognosis at 3 months [14]. Taken together, serum calprotectin may be a biomarker for acute brain injury. Up to now, there is no clinical report with respect to serum calprotectin levels after head trauma. Therefore, this study was designed to determine correlation of serum calprotectin levels with trauma severity, and the applicability of serum calprotectin in predicting poor prognosis in a cohort of sTBI patients.

Section snippets

Design and patients

This is a multiple-center prospective cohort study of consecutive blunt sTBI (postresuscitation GCS score 3–8) patients hospitalized to Affiliated Kunshan Hospital of Jiangsu University, Suzhou Kowloon Hospital and Kunshan Hospital of Traditional Chinese Medicine between January 2017 and July 2019. All patients included in the study were adults (age of 18 years or above) and admitted to hospital within 12 h after trauma. Patients with the following conditions were excluded from the study,

Patient characteristics

Initially, 187 sTBI patients were assessed, whose age was equal to or exceeded 18 years and who was hospitalized within posttraumatic 12 h. Patients were excluded from the study, because of abbreviated injury scale score of 3 or more for any other region (12 cases), unavailable blood sampling (3 cases), incomplete data (2 cases), loss to follow-up (4 cases), previous neurological diseases (9 cases), or systemic inflammation or infection (8 cases). Finally, a total of 149 patients (79.7%) were

Discussion

Serum calprotectin levels were elevated significantly in some noninfectious inflammatory diseases, e.g. arthritis, chronic inflammatory lung disease and intestinal disease [17]. Calprotectin mainly presents in the cytoplasm of inflammatory cells like granulocytes and monocytes [18]. In the central nervous system, calprotectin is abundantly expressed in microvascular endothelial cells and microglial cells [19]. Calprotectin is produced by neutrophils and infiltrating macrophages in the ischemic

Conclusions

Serum calprotectin could be utilized as an independent predictor of mortality and poor outcome at 90 days after sTBI. Also, serum calprotectin levels in sTBI patients have high prognostic predictive capability. Moreover, serum calprotectin levels are closely related to inflammatory reaction after sTBI, substantializing serum calprotectin as an inflammatory, prognostic biomarker of sTBI.

CRediT authorship contribution statement

Yan Yang: Conceptualization, Methodology, Writing - review & editing. Likui Shen: Data curation, Writing - original draft. Min Xu: Visualization, Investigation. Long Chen: Supervision, Software, Validation. Wei Lu: Supervision, Software, Validation. Wenhua Wang: Conceptualization, Methodology, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank all participants for their providing blood samples.

Funding

This work was supported by grants from the suzhou science and technology project (SYS2020067).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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    Y. Yang and L. Shen contributed equally to this work.

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