Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury

Linnéa Lagerstedt; Leire Azurmendi; Olli Tenovuo; Ari J. Katila; Riikka S.K. Takala; Kaj Blennow; Virginia F.J. Newcombe; Henna Riikka Maanpää; Jussi Tallus; Iftakher Hossain; Mark van Gils; David K. Menon; Peter J. Hutchinson; Henrik Zetterberg; Jussi P. Posti; Jean Charles Sanchez

doi:10.3389/fneur.2020.00376

Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury

Linnéa Lagerstedt, Leire Azurmendi, Olli Tenovuo, Ari J. Katila, Riikka S.K. Takala, Kaj Blennow, Virginia F.J. Newcombe, Henna Riikka Maanpää, Jussi Tallus, Iftakher Hossain, Mark van Gils, David K. Menon, Peter J. Hutchinson, Henrik Zetterberg, Jussi P. Posti, Jean Charles Sanchez

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

19 Citations (Scopus)

Abstract

Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

Original language	English
Article number	376
Journal	Frontiers in Neurology
Volume	11
DOIs	https://doi.org/10.3389/fneur.2020.00376
Publication status	Published - 2 Jun 2020
Externally published	Yes
Publication type	A1 Journal article-refereed

Funding

This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Academy of Finland (Grant #17379) (JP), the Government's Special Financial Transfer tied to academic research in Health Sciences (Finland) (JP), the Emil Aaltonen Foundation sr (JP), the Finnish Brain Foundation sr (JP), the Maire Taponen Foundation (JP), the Integra EANS Research Grant (IH), the Academy of Medical Sciences/The Health Foundation Fellowship (VN), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DM), the Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), the Torsten S?derberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, and 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. Dr. Posti has received funding from the Academy of Finland (Grant #17379) and Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). Dr. Posti has also received a grant from the Finnish Brain Foundation, a grant from the Emil Aaltonen Foundation, as well as a grant from the Maire Taponen Foundation.

Keywords

biomarker
heart fatty-acid binding protein
interleukin 10
outcome
panel
protein
traumatic brain injury

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.3389/fneur.2020.00376Licence: CC BY

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Lagerstedt, L., Azurmendi, L., Tenovuo, O., Katila, A. J., Takala, R. S. K., Blennow, K., Newcombe, V. F. J., Maanpää, H. R., Tallus, J., Hossain, I., Gils, M. V., Menon, D. K., Hutchinson, P. J., Zetterberg, H., Posti, J. P., & Sanchez, J. C. (2020). Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury. Frontiers in Neurology, 11, Article 376. https://doi.org/10.3389/fneur.2020.00376

@article{1c3df3bbc51946a5a0183c98bc088efb,

title = "Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury",

abstract = "Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.",

keywords = "biomarker, heart fatty-acid binding protein, interleukin 10, outcome, panel, protein, traumatic brain injury",

author = "Linn{\'e}a Lagerstedt and Leire Azurmendi and Olli Tenovuo and Katila, {Ari J.} and Takala, {Riikka S.K.} and Kaj Blennow and Newcombe, {Virginia F.J.} and Maanp{\"a}{\"a}, {Henna Riikka} and Jussi Tallus and Iftakher Hossain and Gils, {Mark van} and Menon, {David K.} and Hutchinson, {Peter J.} and Henrik Zetterberg and Posti, {Jussi P.} and Sanchez, {Jean Charles}",

note = "Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Academy of Finland (Grant #17379) (JP), the Government's Special Financial Transfer tied to academic research in Health Sciences (Finland) (JP), the Emil Aaltonen Foundation sr (JP), the Finnish Brain Foundation sr (JP), the Maire Taponen Foundation (JP), the Integra EANS Research Grant (IH), the Academy of Medical Sciences/The Health Foundation Fellowship (VN), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DM), the Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), the Torsten S?derberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, and 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. Dr. Posti has received funding from the Academy of Finland (Grant #17379) and Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). Dr. Posti has also received a grant from the Finnish Brain Foundation, a grant from the Emil Aaltonen Foundation, as well as a grant from the Maire Taponen Foundation. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Lagerstedt, Azurmendi, Tenovuo, Katila, Takala, Blennow, Newcombe, Maanp{\"a}{\"a}, Tallus, Hossain, Gils, Menon, Hutchinson, Zetterberg, Posti and Sanchez.",

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month = jun,

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doi = "10.3389/fneur.2020.00376",

language = "English",

volume = "11",

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Lagerstedt, L, Azurmendi, L, Tenovuo, O, Katila, AJ, Takala, RSK, Blennow, K, Newcombe, VFJ, Maanpää, HR, Tallus, J, Hossain, I, Gils, MV, Menon, DK, Hutchinson, PJ, Zetterberg, H, Posti, JP & Sanchez, JC 2020, 'Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury', Frontiers in Neurology, vol. 11, 376. https://doi.org/10.3389/fneur.2020.00376

TY - JOUR

T1 - Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury

AU - Lagerstedt, Linnéa

AU - Azurmendi, Leire

AU - Tenovuo, Olli

AU - Katila, Ari J.

AU - Takala, Riikka S.K.

AU - Blennow, Kaj

AU - Newcombe, Virginia F.J.

AU - Maanpää, Henna Riikka

AU - Tallus, Jussi

AU - Hossain, Iftakher

AU - Gils, Mark van

AU - Menon, David K.

AU - Hutchinson, Peter J.

AU - Zetterberg, Henrik

AU - Posti, Jussi P.

AU - Sanchez, Jean Charles

N1 - Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Academy of Finland (Grant #17379) (JP), the Government's Special Financial Transfer tied to academic research in Health Sciences (Finland) (JP), the Emil Aaltonen Foundation sr (JP), the Finnish Brain Foundation sr (JP), the Maire Taponen Foundation (JP), the Integra EANS Research Grant (IH), the Academy of Medical Sciences/The Health Foundation Fellowship (VN), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DM), the Wallenberg Academy Fellowship and grants from the Swedish and European Research Councils (HZ), the Torsten S?derberg Professorship in Medicine, award by the Royal Swedish Academy of Sciences, and 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. Dr. Posti has received funding from the Academy of Finland (Grant #17379) and Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). Dr. Posti has also received a grant from the Finnish Brain Foundation, a grant from the Emil Aaltonen Foundation, as well as a grant from the Maire Taponen Foundation. Publisher Copyright: © Copyright © 2020 Lagerstedt, Azurmendi, Tenovuo, Katila, Takala, Blennow, Newcombe, Maanpää, Tallus, Hossain, Gils, Menon, Hutchinson, Zetterberg, Posti and Sanchez.

PY - 2020/6/2

Y1 - 2020/6/2

N2 - Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

AB - Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

KW - biomarker

KW - heart fatty-acid binding protein

KW - interleukin 10

KW - outcome

KW - panel

KW - protein

KW - traumatic brain injury

U2 - 10.3389/fneur.2020.00376

DO - 10.3389/fneur.2020.00376

M3 - Article

AN - SCOPUS:85086520769

SN - 1664-2295

VL - 11

JO - Frontiers in Neurology

JF - Frontiers in Neurology

M1 - 376

ER -

Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury

Abstract

Funding

Keywords

ASJC Scopus subject areas

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