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Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis

Nääs, Anja ; Li, Peng ; Ahlm, Clas ; Aurelius, Elisabeth ; Järhult, Josef D. ; Schliamser, Silvia LU ; Studahl, Marie ; Xiao, Wenzhong ; Bergquist, Jonas and Westman, Gabriel LU (2023) In Infectious Diseases 55(10). p.694-705
Abstract

Objectives: We examined the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) during the course of the disease, in relation to anti-N-methyl-D-aspartate receptor (NMDAR) serostatus, corticosteroid treatment, brain MRI and neurocognitive performance. Methods: Patients were retrospectively included from a previous prospective trial with a pre-specified CSF sampling protocol. Mass spectrometry data of the CSF proteome were processed using pathway analysis. Results: We included 48 patients (110 CSF samples). Samples were grouped based on time of collection relative to hospital admission–T1: ≤ 9 d, T2: 13–28 d, T3: ≥ 68 d. At T1, a strong multi-pathway response was seen including acute phase response,... (More)

Objectives: We examined the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) during the course of the disease, in relation to anti-N-methyl-D-aspartate receptor (NMDAR) serostatus, corticosteroid treatment, brain MRI and neurocognitive performance. Methods: Patients were retrospectively included from a previous prospective trial with a pre-specified CSF sampling protocol. Mass spectrometry data of the CSF proteome were processed using pathway analysis. Results: We included 48 patients (110 CSF samples). Samples were grouped based on time of collection relative to hospital admission–T1: ≤ 9 d, T2: 13–28 d, T3: ≥ 68 d. At T1, a strong multi-pathway response was seen including acute phase response, antimicrobial pattern recognition, glycolysis and gluconeogenesis. At T2, most pathways activated at T1 were no longer significantly different from T3. After correction for multiplicity and considering the effect size threshold, 6 proteins were significantly less abundant in anti-NMDAR seropositive patients compared to seronegative: procathepsin H, heparin cofactor 2, complement factor I, protein AMBP, apolipoprotein A1 and polymeric immunoglobulin receptor. No significant differences in individual protein levels were found in relation to corticosteroid treatment, size of brain MRI lesion or neurocognitive performance. Conclusions: We show a temporal change in the CSF proteome in HSE patients during the course of the disease. This study provides insight into quantitative and qualitative aspects of the dynamic pathophysiology and pathway activation patterns in HSE and prompts for future studies on the role of apolipoprotein A1 in HSE, which has previously been associated with NMDAR encephalitis.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apolipoprotein A1, Herpes simplex encephalitis, HSV-1, proteomics
in
Infectious Diseases
volume
55
issue
10
pages
12 pages
publisher
Informa Healthcare
external identifiers
  • pmid:37395107
  • scopus:85164408018
ISSN
2374-4235
DOI
10.1080/23744235.2023.2230281
language
English
LU publication?
yes
id
30eb66b9-abbd-42c2-b79f-ffa376932f54
date added to LUP
2023-10-16 14:49:50
date last changed
2024-04-19 02:25:07
@article{30eb66b9-abbd-42c2-b79f-ffa376932f54,
  abstract     = {{<p>Objectives: We examined the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) during the course of the disease, in relation to anti-N-methyl-D-aspartate receptor (NMDAR) serostatus, corticosteroid treatment, brain MRI and neurocognitive performance. Methods: Patients were retrospectively included from a previous prospective trial with a pre-specified CSF sampling protocol. Mass spectrometry data of the CSF proteome were processed using pathway analysis. Results: We included 48 patients (110 CSF samples). Samples were grouped based on time of collection relative to hospital admission–T1: ≤ 9 d, T2: 13–28 d, T3: ≥ 68 d. At T1, a strong multi-pathway response was seen including acute phase response, antimicrobial pattern recognition, glycolysis and gluconeogenesis. At T2, most pathways activated at T1 were no longer significantly different from T3. After correction for multiplicity and considering the effect size threshold, 6 proteins were significantly less abundant in anti-NMDAR seropositive patients compared to seronegative: procathepsin H, heparin cofactor 2, complement factor I, protein AMBP, apolipoprotein A1 and polymeric immunoglobulin receptor. No significant differences in individual protein levels were found in relation to corticosteroid treatment, size of brain MRI lesion or neurocognitive performance. Conclusions: We show a temporal change in the CSF proteome in HSE patients during the course of the disease. This study provides insight into quantitative and qualitative aspects of the dynamic pathophysiology and pathway activation patterns in HSE and prompts for future studies on the role of apolipoprotein A1 in HSE, which has previously been associated with NMDAR encephalitis.</p>}},
  author       = {{Nääs, Anja and Li, Peng and Ahlm, Clas and Aurelius, Elisabeth and Järhult, Josef D. and Schliamser, Silvia and Studahl, Marie and Xiao, Wenzhong and Bergquist, Jonas and Westman, Gabriel}},
  issn         = {{2374-4235}},
  keywords     = {{apolipoprotein A1; Herpes simplex encephalitis; HSV-1; proteomics}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{694--705}},
  publisher    = {{Informa Healthcare}},
  series       = {{Infectious Diseases}},
  title        = {{Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis}},
  url          = {{http://dx.doi.org/10.1080/23744235.2023.2230281}},
  doi          = {{10.1080/23744235.2023.2230281}},
  volume       = {{55}},
  year         = {{2023}},
}