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Short-term biological variation of serum glial fibrillary acidic protein

  • Silje Hovden Christensen , Claus Vinter Bødker Hviid , Anne Tranberg Madsen ORCID logo , Tina Parkner and Anne Winther-Larsen EMAIL logo
Published/Copyright: August 15, 2022

Abstract

Objectives

Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker for intracerebral diseases and is approved for clinical use in traumatic brain injury. GFAP is also being investigated for several other applications, where the GFAP changes are not always outstanding. It is thus essential for the interpretation of GFAP to distinguish clinical relevant changes from natural occurring biological variation. This study aimed at estimating the biological variation of serum GFAP.

Methods

Apparently healthy subjects (n=33) had blood sampled for three consecutive days. On the second day, blood was also drawn every third hour from 9 AM to 9 PM. Serum GFAP was measured by Single Molecule Array (Simoa™). Components of biological variation were estimated in a linear mixed-effects model.

Results

The overall median GFAP value was 92.5 pg/mL (range 34.4–260.3 pg/mL). The overall within– (CVI) and between-subject variations (CVG) were 9.7 and 39.5%. The reference change value was 36.9% for an increase. No day-to-day variation was observed, however semidiurnal variation was observed with increasing GFAP values between 9 AM and 12 PM (p<0.00001) and decreasing from 12 to 9 PM (p<0.001).

Conclusions

Serum GFAP exhibits a relatively low CVI but a considerable CVG and a marked semidiurnal variation. This implies caution on the timing of blood sampling and when interpreting GFAP in relation to reference intervals, especially in conditions where only small GFAP differences are observed.


Corresponding author: Anne Winther-Larsen, MD, PhD, Associated Professor, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Aarhus, Denmark; and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Phone: +0045 7844 0000, E-mail:

Funding source: Dagmar Marshalls Fond

Funding source: Harboefonden

Acknowledgments

The authors wish to thank the biomedical laboratory technicians at the research department of the Department of Clinical Biochemistry, Aarhus University Hospital.

  1. Research funding: The work was supported by Harboefonden and Dagmar Marshalls Fond. The funders did not have any role in the study design, data collection, data analysis, interpretation, or writing of the report.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflicts of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Central Denmark Region Committees on Biomedical Research Ethics (1-10-72-452-17).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0480).


Received: 2022-05-17
Accepted: 2022-07-29
Published Online: 2022-08-15
Published in Print: 2022-10-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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