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Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

Bakochi, Anahita LU ; Mohanty, Tirthankar LU ; Pyl, Paul Theodor LU ; Gueto-Tettay, Carlos Alberto LU ; Malmström, Lars LU ; Linder, Adam LU and Malmström, Johan LU (2021) In eLife 10.
Abstract

Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in... (More)

Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.

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; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
eLife
volume
10
publisher
eLife Sciences Publications LTD.
external identifiers
  • scopus:85104276699
  • pmid:33821792
ISSN
2050-084X
DOI
10.7554/eLife.64159
language
English
LU publication?
yes
id
5e893f6a-b837-4735-95b2-d602fa272fc6
date added to LUP
2021-04-11 22:10:54
date last changed
2021-06-16 01:13:59
@article{5e893f6a-b837-4735-95b2-d602fa272fc6,
  abstract     = {<p>Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.</p>},
  author       = {Bakochi, Anahita and Mohanty, Tirthankar and Pyl, Paul Theodor and Gueto-Tettay, Carlos Alberto and Malmström, Lars and Linder, Adam and Malmström, Johan},
  issn         = {2050-084X},
  language     = {eng},
  month        = {04},
  publisher    = {eLife Sciences Publications LTD.},
  series       = {eLife},
  title        = {Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis},
  url          = {http://dx.doi.org/10.7554/eLife.64159},
  doi          = {10.7554/eLife.64159},
  volume       = {10},
  year         = {2021},
}