Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis

Frontiers in Immunology

Immunology

Mauro Truglio¹  Annunziata Stefanile¹  Laura Conti¹  Giovanna D’Agosto²  Andrea Maialetti³  Marta Maschio³  Silvana Zannino³  Edvina Galiè³  Maria Cellerino⁴  Marco Fiorelli⁵  Antonio Cortese⁵  Svetlana Lorenzano⁵  Marco Salvetti⁶  Caterina Lapucci⁷  Matilde Inglese⁸  Tatiana Koudriavtseva⁹  Maria Maddalena Filippi^1,10  Carlo Piantadosi^1,11 

[1] Clinical Pathology and Cancer Biobank, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy;Clinical Pathology and Microbiology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gallicano Dermatological 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;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;Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy;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;Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy;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;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;Neuroscience and Imaging, Fatebenefratelli Hospital, Rome, Italy;Unità Operativa Complessa (UOC) Neurology, San Giovanni-Addolorata Hospital, Rome, Italy;

关键词: multiple sclerosis;    relapse;    tissue factor;    biomarker;    coagulation;   

DOI  :  10.3389/fimmu.2023.1226616

 received in 2023-05-21, accepted in 2023-07-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectivesRecent 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.MethodsWe 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.ResultsCompared 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.ConclusionTissue-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 registrationClinicalTrials.gov, identifier NCT04380220.

【 授权许可】

Unknown   
Copyright © 2023 Koudriavtseva, Lorenzano, Cellerino, Truglio, Fiorelli, Lapucci, D’Agosto, Conti, Stefanile, Zannino, Filippi, Cortese, Piantadosi, Maschio, Maialetti, Galiè, Salvetti and Inglese