Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.

<h4>Introduction</h4>Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compa...

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Main Authors: Charles M Manyelo, Novel N Chegou, James A Seddon, Candice I Snyders, Hygon Mutavhatsindi, Portia M Manngo, Gerhard Walzl, Kim Stanley, Regan S Solomons
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250944&type=printable
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author Charles M Manyelo
Novel N Chegou
James A Seddon
Candice I Snyders
Hygon Mutavhatsindi
Portia M Manngo
Gerhard Walzl
Kim Stanley
Regan S Solomons
author_facet Charles M Manyelo
Novel N Chegou
James A Seddon
Candice I Snyders
Hygon Mutavhatsindi
Portia M Manngo
Gerhard Walzl
Kim Stanley
Regan S Solomons
author_sort Charles M Manyelo
collection DOAJ
description <h4>Introduction</h4>Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke.<h4>Methods</h4>We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants.<h4>Results</h4>After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity.<h4>Conclusion</h4>Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.
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spelling doaj-art-a742ba5451b64bcb83bb927ce3772d442025-08-20T02:31:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e025094410.1371/journal.pone.0250944Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.Charles M ManyeloNovel N ChegouJames A SeddonCandice I SnydersHygon MutavhatsindiPortia M ManngoGerhard WalzlKim StanleyRegan S Solomons<h4>Introduction</h4>Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke.<h4>Methods</h4>We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants.<h4>Results</h4>After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity.<h4>Conclusion</h4>Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250944&type=printable
spellingShingle Charles M Manyelo
Novel N Chegou
James A Seddon
Candice I Snyders
Hygon Mutavhatsindi
Portia M Manngo
Gerhard Walzl
Kim Stanley
Regan S Solomons
Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
PLoS ONE
title Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
title_full Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
title_fullStr Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
title_full_unstemmed Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
title_short Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.
title_sort serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250944&type=printable
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