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

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Blood Proteins/*analysis ; Cerebrospinal Fluid Proteins/*analysis ; Stroke/*blood ; Stroke/*cerebrospinal fluid ; Tuberculosis, Meningeal/*blood ; Tuberculosis, Meningeal/*cerebrospinal fluid; Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Mycobacterium tuberculosis/isolation & purification ; Pilot Projects ; ROC Curve ; South Africa ; Stroke/diagnosis ; Stroke/etiology ; Tuberculosis, Meningeal/microbiology
    • 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.
      Competing Interests: NC, CM, GW and RS are listed as inventors on an International Patent Application entitled “Cerebrospinal fluid and blood-based biomarkers for the diagnosis of tuberculosis meningitis” (PCT/IB2019/054259), filing date: 23 May 2019. NC and GW are listed as inventors on another patent application entitled “Method for diagnosing tuberculous meningitis” (PCT/IB2015/052751), filing date: 15 April 2015. These applications do not generate any royalties for the inventors. These does not alter our adherence to PLOS ONE policies on sharing data and materials.
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    • Grant Information:
      MR/R007942/1 United Kingdom MRC_ Medical Research Council
    • Accession Number:
      0 (Biomarkers)
      0 (Blood Proteins)
      0 (Cerebrospinal Fluid Proteins)
    • Publication Date:
      Date Created: 20210430 Date Completed: 20211020 Latest Revision: 20220317
    • Publication Date:
      20240105
    • Accession Number:
      PMC8087017
    • Accession Number:
      10.1371/journal.pone.0250944
    • Accession Number:
      33930055