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. 2019 Jan 1;36(1):182-187.
doi: 10.1089/neu.2017.5623. Epub 2018 Jul 23.

Performance Evaluation of a Multiplex Assay for Simultaneous Detection of Four Clinically Relevant Traumatic Brain Injury Biomarkers

Frederick K Korley  1 , John K Yue  2 , David H Wilson  3 , Kevin Hrusovsky  3 , Ramon Diaz-Arrastia  4 , Adam R Ferguson  2 , Esther L Yuh  5 , Pratik Mukherjee  5 , Kevin K W Wang  6 , Alex B Valadka  7 , Ava M Puccio  8 , David O Okonkwo  8 , Geoffrey T Manley  2
Affiliations

Performance Evaluation of a Multiplex Assay for Simultaneous Detection of Four Clinically Relevant Traumatic Brain Injury Biomarkers

Frederick K Korley et al. J Neurotrauma. .

Abstract

Traumatic brain injury (TBI) results in heterogeneous pathology affecting multiple cells and tissue types in the brain. It is likely that assessment of such complexity will require simultaneous measurement of multiple molecular biomarkers in a single sample of biological fluid. We measured glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NF-L) and total tau in plasma samples obtained from 107 subjects enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) Study using the Quanterix Simoa 4-Plex assay. We also measured NF-L using the Simoa singleplex assay. We computed the correlation between the different biomarkers and calculated the discriminative value of each biomarker for distinguishing between subjects with abnormal versus normal head computed tomography (CT). We found a strong correlation between NF-L values derived from the multiplex and singleplex assays (correlation coefficient = 0.997). Among biomarker values derived from the multiplex assay, the strongest correlation was between the axonal and neuronal markers, NF-L and UCH-L1 (coefficient = 0.71). The weakest correlation was between the glial marker GFAP and the axonal marker tau (coefficient = 0.06). The areas under the curves for distinguishing between subjects with/without abnormal head CT for multiplex GFAP, UCH-L1, NF-L, and total tau were: 0.88 (95% confidence interval 0.81-0.95), 0.86 (0.79-0.93), 0.84 (0.77-0.92), and 0.77 0.67-0.86), respectively. We conclude that the multiplex assay provides simultaneous quantification of GFAP, UCH-L1, NF-L, and tau, and may be clinically useful in the diagnosis of TBI as well as identifying different types of cellular injury.

Keywords: biomarkers; glial fibrillary acidic protein; multiplex immunoassay; neurofilament light chain; total tau; traumatic brain injury; ubiquitin c-terminal hydrolase L1.

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Conflict of interest statement

David H. Wilson and Kevin Hrusovsky are employees of Quanterix Corporation, which manufactures the multiplex assay studied. For the remaining authors, no competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Distribution of plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau, and neurofilament light chain (NF-L) levels according to head computed tomography (CT) findings. Plasma levels of GFAP, UCH-L1, total tau, and NF-L were higher in subjects with traumatic intracranial abnormality seen on head CT than subjects with normal head CT scans.
<b>FIG. 2.</b>
FIG. 2.
Discriminative ability of each of the biomarkers examined for distinguishing between those with normal and abnormal head computed tomography (CT) scans. Receiver operator curve illustrating the discriminative value of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau, and neurofilament light chain (NF-L) for distinguishing between subjects with traumatic intracranial lesions on head CT and those without such lesions. Color image is available online at www.liebertpub.com/neu
See this image and copyright information in PMC

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