학술논문
Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis.
Document Type
Academic Journal
Author
Koudriavtseva T; Medical Direction, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy.; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Lorenzano S; Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.; Cellerino M; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.; Truglio M; Clinical Pathology and Cancer Biobank, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy.; Fiorelli M; Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.; Lapucci C; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.; D'Agosto G; Clinical Pathology and Microbiology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gallicano Dermatological Institute, Rome, Italy.; Conti L; Clinical Pathology and Cancer Biobank, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy.; Stefanile A; Clinical Pathology and Cancer Biobank, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy.; Zannino S; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Filippi MM; Neuroscience and Imaging, Fatebenefratelli Hospital, Rome, Italy.; Cortese A; Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.; Piantadosi C; Unità Operativa Complessa (UOC) Neurology, San Giovanni-Addolorata Hospital, Rome, Italy.; Maschio M; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Maialetti A; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Galiè E; Department of Clinical Experimental Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy.; Salvetti M; Department of Neuroscience Mental Health and Sensory Organs (NEMOS), Sapienza University, Rome, Italy.; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.; Inglese M; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.; Department of Neurology, Mount Sinai Hospital, New York, NY, United States.
Source
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
Objectives: Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.
Methods: We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission ( n =30; 23F/7M, 40 ± 8.14 years) or a relapse ( n =30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls ( n =30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.
Results: Compared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.
Conclusion: Tissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.
Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04380220.
Competing Interests: TK: received grant from Italian Ministry of Health. MC: received consulting fees from Zambon, support for attending meetings/travel from Janssen. MF: received part of grant from Italian Ministry of Health. MM: received honoraria for presentation/manuscript writing and support for attending meetings/travel from EISAI. MS: received grant from FISM; speaking honoraria from Merck, Sanofi, Novartis, Roche, Viatris, Biogen, BMS; support for patents IT 1417523 and EP2981625. MI: received consulting fees from Biogen, Novartis Merck, Sanofi, Roche, BMS, Janssen; received honoraria for presentation from Biogen, Novartis Merck, Sanofi, Roche, BMS, Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Koudriavtseva, Lorenzano, Cellerino, Truglio, Fiorelli, Lapucci, D’Agosto, Conti, Stefanile, Zannino, Filippi, Cortese, Piantadosi, Maschio, Maialetti, Galiè, Salvetti and Inglese.)
Methods: We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission ( n =30; 23F/7M, 40 ± 8.14 years) or a relapse ( n =30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls ( n =30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.
Results: Compared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.
Conclusion: Tissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.
Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04380220.
Competing Interests: TK: received grant from Italian Ministry of Health. MC: received consulting fees from Zambon, support for attending meetings/travel from Janssen. MF: received part of grant from Italian Ministry of Health. MM: received honoraria for presentation/manuscript writing and support for attending meetings/travel from EISAI. MS: received grant from FISM; speaking honoraria from Merck, Sanofi, Novartis, Roche, Viatris, Biogen, BMS; support for patents IT 1417523 and EP2981625. MI: received consulting fees from Biogen, Novartis Merck, Sanofi, Roche, BMS, Janssen; received honoraria for presentation from Biogen, Novartis Merck, Sanofi, Roche, BMS, Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Koudriavtseva, Lorenzano, Cellerino, Truglio, Fiorelli, Lapucci, D’Agosto, Conti, Stefanile, Zannino, Filippi, Cortese, Piantadosi, Maschio, Maialetti, Galiè, Salvetti and Inglese.)