Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-Remitting Multiple Sclerosis.
Biomarkers
Blood Coagulation
/ immunology
Blood Coagulation Factors
/ metabolism
Cerebrovascular Circulation
Clinical Protocols
Complement Activation
/ immunology
Complement System Proteins
/ immunology
Disease Susceptibility
Gene Expression Profiling
Humans
Magnetic Resonance Imaging
/ methods
Multiple Sclerosis, Relapsing-Remitting
/ blood
cerebral hypoperfusion
coagulation
complement
infection
multiple sclerosis
platelets
relapse
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
04
2020
accepted:
25
08
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
15
5
2021
Statut:
epublish
Résumé
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism "immunothrombosis" linking inflammation and coagulation. Moreover, decreased cerebral blood volume (CBV), cerebral blood flow (CBF), and prolonged mean transit time (MTT) have been widely demonstrated by MRI in MS patients. We hypothesized that coagulation/complement and platelet activation during MS relapse, likely during viral infections, could be related to CBF decrease. Our specific aims are to evaluate whether there are differences in serum/plasma levels of coagulation/complement factors between relapsing-remitting (RR) MS patients (RRMS) in relapse and those in remission and healthy controls as well as to assess whether brain hemodynamic changes detected by MRI occur in relapse compared with remission. This will allow us to correlate coagulation status with perfusion and demographic/clinical features in MS patients. This is a multi-center, prospective, controlled study. RRMS patients (1° group: 30 patients in relapse; 2° group: 30 patients in remission) and age/sex-matched controls (3° group: 30 subjects) will be enrolled in the study. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, PT, aPTT, fibrinogen, factor II, VIII, and X, D-dimer, antithrombin, protein C, protein S, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays, or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number, and volume. ANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05. Identifying a link between activation of coagulation/complement system and cerebral hypoperfusion could improve the identification of novel molecular and/or imaging biomarkers and targets, leading to the development of new effective therapeutic strategies in MS. Clinicaltrials.gov, identifier NCT04380220.
Identifiants
pubmed: 33193314
doi: 10.3389/fimmu.2020.548604
pmc: PMC7655134
doi:
Substances chimiques
Biomarkers
0
Blood Coagulation Factors
0
Complement System Proteins
9007-36-7
Banques de données
ClinicalTrials.gov
['NCT04380220']
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
548604Informations de copyright
Copyright © 2020 Koudriavtseva, Stefanile, Fiorelli, Lapucci, Lorenzano, Zannino, Conti, D’Agosto, Pimpinelli, Di Domenico, Mandoj, Giannarelli, Donzelli, Blandino, Salvetti and Inglese.
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