Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis
Author(s)
Type
Journal Article
Abstract
Introduction 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. Methods 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. Results 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. Conclusion 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.
Date Issued
2021-04-30
Online Publication Date
2022-01-28T15:54:14Z
Date Acceptance
2021-04-19
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
18
Journal / Book Title
PLoS One
Volume
16
Issue
4
Copyright Statement
© 2021 Manyelo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URI
Identifier
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250944
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000664607000054&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PATHOGENESIS
DIAGNOSIS
BRAIN
BIOMARKERS
ADAMTS13
DISEASE
Biomarkers
Blood Proteins
Cerebrospinal Fluid Proteins
Child, Preschool
Female
Humans
Infant
Male
Mycobacterium tuberculosis
Pilot Projects
ROC Curve
South Africa
Stroke
Tuberculosis, Meningeal
Humans
Mycobacterium tuberculosis
Tuberculosis, Meningeal
Blood Proteins
Cerebrospinal Fluid Proteins
Pilot Projects
ROC Curve
Child, Preschool
Infant
South Africa
Female
Male
Stroke
Biomarkers
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PATHOGENESIS
DIAGNOSIS
BRAIN
BIOMARKERS
ADAMTS13
DISEASE
General Science & Technology
Publication Status
Published
Article Number
ARTN e0250944
Date Publish Online
2021-04-30