Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV

C. Blokhuis, C. F. W. Peeters, S. Cohen, H. J. Scherpbier, T. W. Kuijpers, P. Reiss, N. A. Kootstra, C. E. Teunissen, D. Pajkrt

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8–18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.
Original languageEnglish
Article number8004
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

@article{ec4510b03b834475b7b6b8b8d31da802,
title = "Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV",
abstract = "Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8–18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.",
author = "C. Blokhuis and Peeters, {C. F. W.} and S. Cohen and Scherpbier, {H. J.} and Kuijpers, {T. W.} and P. Reiss and Kootstra, {N. A.} and Teunissen, {C. E.} and D. Pajkrt",
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doi = "10.1038/s41598-019-44198-z",
language = "English",
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Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV. / Blokhuis, C.; Peeters, C. F. W.; Cohen, S.; Scherpbier, H. J.; Kuijpers, T. W.; Reiss, P.; Kootstra, N. A.; Teunissen, C. E.; Pajkrt, D.

In: Scientific Reports, Vol. 9, No. 1, 8004, 01.12.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Blokhuis, C.

AU - Peeters, C. F. W.

AU - Cohen, S.

AU - Scherpbier, H. J.

AU - Kuijpers, T. W.

AU - Reiss, P.

AU - Kootstra, N. A.

AU - Teunissen, C. E.

AU - Pajkrt, D.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8–18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.

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