Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis
(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.
(Less)
- author
- Nääs, Anja ; Li, Peng ; Ahlm, Clas ; Aurelius, Elisabeth ; Järhult, Josef D. ; Schliamser, Silvia LU ; Studahl, Marie ; Xiao, Wenzhong ; Bergquist, Jonas and Westman, Gabriel LU
- organization
- publishing date
- 2023
- 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
-
- scopus:85164408018
- pmid:37395107
- 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
- 2024-09-06 15:41:02
@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}}, }