The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis.
Biomarker
Cerebrospinal fluid
Degeneration
Dimethyl fumarate
HTRA1
Mitoxantrone
Multiple sclerosis
Secondary progression
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
26
12
2020
accepted:
22
02
2021
revised:
19
02
2021
pubmed:
5
3
2021
medline:
14
8
2021
entrez:
4
3
2021
Statut:
ppublish
Résumé
High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease.
OBJECTIVE
OBJECTIVE
Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue.
METHODS
METHODS
Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map.
RESULTS
RESULTS
HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons.
CONCLUSION
CONCLUSIONS
HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.
Identifiants
pubmed: 33661357
doi: 10.1007/s00415-021-10489-7
pii: 10.1007/s00415-021-10489-7
doi:
Substances chimiques
Biomarkers
0
High-Temperature Requirement A Serine Peptidase 1
EC 3.4.21.-
HTRA1 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3316-3324Informations de copyright
© 2021. Springer-Verlag GmbH, DE part of Springer Nature.
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