Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury

Jussi P. Posti; Riikka S.K. Takala; Linneá Lagerstedt; Alex M. Dickens; Iftakher Hossain; Mehrbod Mohammadian; Henna Ala-Seppälä; Janek Frantzén; Mark Van Gils; Peter J. Hutchinson; Ari J. Katila; Henna Riikka Maanpaä; David K. Menon; Virginia F. Newcombe; Jussi Tallus; Kevin Hrusovsky; David H. Wilson; Jessica Gill; Jean Charles Sanchez; Olli Tenovuo; Henrik Zetterberg; Kaj Blennow

doi:10.1089/neu.2018.6254

Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury

Jussi P. Posti, Riikka S.K. Takala, Linneá Lagerstedt, Alex M. Dickens, Iftakher Hossain, Mehrbod Mohammadian, Henna Ala-Seppälä, Janek Frantzén, Mark Van Gils, Peter J. Hutchinson, Ari J. Katila, Henna Riikka Maanpaä, David K. Menon, Virginia F. Newcombe, Jussi Tallus, Kevin Hrusovsky, David H. Wilson, Jessica Gill, Jean Charles Sanchez, Olli TenovuoHenrik Zetterberg, Kaj Blennow

Research output: Contribution to journal › Article › Scientific › peer-review

52 Citations (Scopus)

Abstract

The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.

Original language	English
Pages (from-to)	2178-2189
Number of pages	12
Journal	Journal of Neurotrauma
Volume	36
Issue number	14
DOIs	https://doi.org/10.1089/neu.2018.6254
Publication status	Published - 15 Jul 2019
Externally published	Yes
Publication type	Not Eligible

Funding

Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), National Institute for Health Research (NIHR) Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre; DKM); Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). The authors thank our research nurses Patricia Bertenyi and Satu Honkala for their valuable contribution to this study. Riikka S.K. Takala has no competing financial interests. RSKT has received speakers’ fees from Abbott, Fresenius-Kabi, Orion corporation and UCB, conference funding from Pfizer and Ster-ipolar and is stockholder of Orion. This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland; JPP), Emil Aaltonen Foundation sr ( JPP), Finnish Brain Foundation sr ( JPP), Maire Taponen Funding: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) ( JPP), Emil Aaltonen Foundation ( JPP), Finnish Brain Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB).

Keywords

biomarkers
computed tomography
traumatic brain injury

ASJC Scopus subject areas

Clinical Neurology

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10.1089/neu.2018.6254

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Posti, J. P., Takala, R. S. K., Lagerstedt, L., Dickens, A. M., Hossain, I., Mohammadian, M., Ala-Seppälä, H., Frantzén, J., Van Gils, M., Hutchinson, P. J., Katila, A. J., Maanpaä, H. R., Menon, D. K., Newcombe, V. F., Tallus, J., Hrusovsky, K., Wilson, D. H., Gill, J., Sanchez, J. C., ... Blennow, K. (2019). Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury. Journal of Neurotrauma, 36(14), 2178-2189. https://doi.org/10.1089/neu.2018.6254

@article{6fa1ca53c1564e2cb77d2bc05a42003f,

title = "Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury",

abstract = "The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.",

keywords = "biomarkers, computed tomography, traumatic brain injury",

author = "Posti, {Jussi P.} and Takala, {Riikka S.K.} and Linne{\'a} Lagerstedt and Dickens, {Alex M.} and Iftakher Hossain and Mehrbod Mohammadian and Henna Ala-Sepp{\"a}l{\"a} and Janek Frantz{\'e}n and {Van Gils}, Mark and Hutchinson, {Peter J.} and Katila, {Ari J.} and Maanpa{\"a}, {Henna Riikka} and Menon, {David K.} and Newcombe, {Virginia F.} and Jussi Tallus and Kevin Hrusovsky and Wilson, {David H.} and Jessica Gill and Sanchez, {Jean Charles} and Olli Tenovuo and Henrik Zetterberg and Kaj Blennow",

note = "Funding Information: Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), National Institute for Health Research (NIHR) Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre; DKM); Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten S{\"o}derberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). The authors thank our research nurses Patricia Bertenyi and Satu Honkala for their valuable contribution to this study. Funding Information: Riikka S.K. Takala has no competing financial interests. RSKT has received speakers{\textquoteright} fees from Abbott, Fresenius-Kabi, Orion corporation and UCB, conference funding from Pfizer and Ster-ipolar and is stockholder of Orion. Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government{\textquoteright}s Special Financial Transfer tied to academic research in Health Sciences (Finland; JPP), Emil Aaltonen Foundation sr ( JPP), Finnish Brain Foundation sr ( JPP), Maire Taponen Funding Information: Funding: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government{\textquoteright}s Special Financial Transfer tied to academic research in Health Sciences (Finland) ( JPP), Emil Aaltonen Foundation ( JPP), Finnish Brain Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten S{\"o}derberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). Publisher Copyright: {\textcopyright} 2019 Mary Ann Liebert, Inc., publishers.",

year = "2019",

month = jul,

day = "15",

doi = "10.1089/neu.2018.6254",

language = "English",

volume = "36",

pages = "2178--2189",

journal = "Journal of Neurotrauma",

issn = "0897-7151",

publisher = "Mary Ann Liebert Inc.",

number = "14",

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Posti, JP, Takala, RSK, Lagerstedt, L, Dickens, AM, Hossain, I, Mohammadian, M, Ala-Seppälä, H, Frantzén, J, Van Gils, M, Hutchinson, PJ, Katila, AJ, Maanpaä, HR, Menon, DK, Newcombe, VF, Tallus, J, Hrusovsky, K, Wilson, DH, Gill, J, Sanchez, JC, Tenovuo, O, Zetterberg, H & Blennow, K 2019, 'Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury', Journal of Neurotrauma, vol. 36, no. 14, pp. 2178-2189. https://doi.org/10.1089/neu.2018.6254

TY - JOUR

T1 - Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury

AU - Posti, Jussi P.

AU - Takala, Riikka S.K.

AU - Lagerstedt, Linneá

AU - Dickens, Alex M.

AU - Hossain, Iftakher

AU - Mohammadian, Mehrbod

AU - Ala-Seppälä, Henna

AU - Frantzén, Janek

AU - Van Gils, Mark

AU - Hutchinson, Peter J.

AU - Katila, Ari J.

AU - Maanpaä, Henna Riikka

AU - Menon, David K.

AU - Newcombe, Virginia F.

AU - Tallus, Jussi

AU - Hrusovsky, Kevin

AU - Wilson, David H.

AU - Gill, Jessica

AU - Sanchez, Jean Charles

AU - Tenovuo, Olli

AU - Zetterberg, Henrik

AU - Blennow, Kaj

N1 - Funding Information: Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), National Institute for Health Research (NIHR) Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre; DKM); Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). The authors thank our research nurses Patricia Bertenyi and Satu Honkala for their valuable contribution to this study. Funding Information: Riikka S.K. Takala has no competing financial interests. RSKT has received speakers’ fees from Abbott, Fresenius-Kabi, Orion corporation and UCB, conference funding from Pfizer and Ster-ipolar and is stockholder of Orion. Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland; JPP), Emil Aaltonen Foundation sr ( JPP), Finnish Brain Foundation sr ( JPP), Maire Taponen Funding Information: Funding: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) ( JPP), Emil Aaltonen Foundation ( JPP), Finnish Brain Foundation ( JPP), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), Torsten Söderberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, grants from the Swedish Research Council (KB). Publisher Copyright: © 2019 Mary Ann Liebert, Inc., publishers.

PY - 2019/7/15

Y1 - 2019/7/15

N2 - The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.

AB - The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.

KW - biomarkers

KW - computed tomography

KW - traumatic brain injury

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DO - 10.1089/neu.2018.6254

M3 - Article

C2 - 30760178

AN - SCOPUS:85068507796

SN - 0897-7151

VL - 36

SP - 2178

EP - 2189

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

IS - 14

ER -

Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury

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