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

Jussi P. Posti (Corresponding Author), 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 journalArticleScientificpeer-review

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 languageEnglish
Pages (from-to)2178-2189
JournalJournal of Neurotrauma
Volume36
Issue number14
DOIs
Publication statusPublished - 15 Jul 2019
MoE publication typeA1 Journal article-refereed

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Biomarkers
Tomography
Glial Fibrillary Acidic Protein
Intermediate Filaments
Fatty Acid-Binding Proteins
Area Under Curve
Light
Glasgow Coma Scale
Interleukin-10
Traumatic Brain Injury
Sensitivity and Specificity
Calcium-Binding Proteins
Immunoassay
Amyloid
ROC Curve
Brain Injuries
Protein Isoforms
Proteins

Keywords

  • biomarkers
  • computed tomography
  • traumatic brain injury

Cite this

Posti, J. P., Takala, R. S. K., Lagerstedt, L., Dickens, A. M., Hossain, I., Mohammadian, M., ... 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
Posti, Jussi P. ; Takala, Riikka S.K. ; Lagerstedt, Linneá ; Dickens, Alex M. ; Hossain, Iftakher ; Mohammadian, Mehrbod ; Ala-Seppälä, Henna ; Frantzén, Janek ; van Gils, Mark ; Hutchinson, Peter J. ; Katila, Ari J. ; Maanpaä, Henna Riikka ; Menon, David K. ; Newcombe, Virginia F. ; Tallus, Jussi ; Hrusovsky, Kevin ; Wilson, David H. ; Gill, Jessica ; Sanchez, Jean Charles ; Tenovuo, Olli ; Zetterberg, Henrik ; Blennow, Kaj. / Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury. In: Journal of Neurotrauma. 2019 ; Vol. 36, No. 14. pp. 2178-2189.
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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.",
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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",
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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

Correlation of blood biomarkers and biomarker panels with traumatic findings on computed tomography after traumatic brain injury. / Posti, Jussi P. (Corresponding Author); Takala, Riikka S.K.; Lagerstedt, Linneá; Dickens, Alex M.; Hossain, Iftakher; Mohammadian, Mehrbod; Ala-Seppälä, Henna; Frantzén, Janek; van Gils, Mark; Hutchinson, Peter J.; Katila, Ari J.; Maanpaä, Henna Riikka; Menon, David K.; Newcombe, Virginia F.; Tallus, Jussi; Hrusovsky, Kevin; Wilson, David H.; Gill, Jessica; Sanchez, Jean Charles; Tenovuo, Olli; Zetterberg, Henrik; Blennow, Kaj.

In: Journal of Neurotrauma, Vol. 36, No. 14, 15.07.2019, p. 2178-2189.

Research output: Contribution to journalArticleScientificpeer-review

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

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.

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