TY - JOUR
T1 - Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-Remitting Multiple Sclerosis
AU - Koudriavtseva, Tatiana
AU - Stefanile, Annunziata
AU - Fiorelli, Marco
AU - Lapucci, Caterina
AU - Lorenzano, Svetlana
AU - Zannino, Silvana
AU - Conti, Laura
AU - D’Agosto, Giovanna
AU - Pimpinelli, Fulvia
AU - Di Domenico, Enea Gino
AU - Mandoj, Chiara
AU - Giannarelli, Diana
AU - Donzelli, Sara
AU - Blandino, Giovanni
AU - Salvetti, Marco
AU - Inglese, Matilde
N1 - Publisher Copyright:
© Copyright © 2020 Koudriavtseva, Stefanile, Fiorelli, Lapucci, Lorenzano, Zannino, Conti, D’Agosto, Pimpinelli, Di Domenico, Mandoj, Giannarelli, Donzelli, Blandino, Salvetti and Inglese.
PY - 2020/10/27
Y1 - 2020/10/27
N2 - Introduction: 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. Materials and Methods: 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. Statistical Analysis: ANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05. Discussion: 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. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04380220.
AB - Introduction: 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. Materials and Methods: 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. Statistical Analysis: ANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05. Discussion: 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. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04380220.
KW - cerebral hypoperfusion
KW - coagulation
KW - complement
KW - infection
KW - multiple sclerosis
KW - platelets
KW - relapse
UR - http://www.scopus.com/inward/record.url?scp=85095933782&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.548604
DO - 10.3389/fimmu.2020.548604
M3 - Article
C2 - 33193314
AN - SCOPUS:85095933782
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 548604
ER -