Plasma levels of protein C pathway proteins and brain magnetic resonance imaging volumes in multiple sclerosis.
Adult
Brain
/ diagnostic imaging
Cross-Sectional Studies
Disease Progression
Endothelial Protein C Receptor
/ genetics
Female
Gray Matter
/ diagnostic imaging
Humans
Magnetic Resonance Imaging
/ methods
Male
Middle Aged
Multiple Sclerosis
/ diagnostic imaging
Protein C
/ analysis
Protein S
/ analysis
Signal Transduction
Treatment Outcome
MRI
coagulation
coagulation inhibitors
multiple sclerosis
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
12
07
2019
accepted:
05
08
2019
pubmed:
14
8
2019
medline:
15
12
2020
entrez:
14
8
2019
Statut:
ppublish
Résumé
The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.
Sections du résumé
BACKGROUND AND PURPOSE
The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients.
METHODS
In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients.
RESULTS
There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only.
CONCLUSIONS
Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.
Identifiants
pubmed: 31408242
doi: 10.1111/ene.14058
pmc: PMC7058813
mid: NIHMS1046115
doi:
Substances chimiques
Endothelial Protein C Receptor
0
PROCR protein, human
0
Protein C
0
Protein S
0
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
235-243Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001412
Pays : United States
Organisme : Jacquemin Family Foundation
Pays : International
Organisme : Emilia Romagna Region, Italy
ID : 1786/2012
Pays : International
Organisme : Annette Funicello Research Fund for Neurological Diseases
Pays : International
Informations de copyright
© 2019 European Academy of Neurology.
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