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.
Front Immunol. 2023 Jul 31;14:1226616. doi: 10.3389/fimmu.2023.1226616. eCollection 2023.
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.
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 (=30; 23F/7M, 40 ± 8.14 years) or a relapse (=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (=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.
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.
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.
ClinicalTrials.gov, identifier NCT04380220.
最近的研究支持凝血参与多发性硬化症，这是一种中枢神经系统的炎症脱髓鞘和退行性疾病。本观察性研究的主要目的是确定多发性硬化症发病机制中最具特异性的促凝/血管因子，并将其与脑血液动力学异常相关联。
我们比较了 i）处于临床缓解期（=30；23 名女性/7 名男性，40±8.14 岁）或复发期（=30；24 名女性/6 名男性，年龄 41±10.74 岁）的多发性硬化症患者与年龄/性别匹配的对照组（=30；23 名女性/7 名男性，40±8.38 岁）的血清/血浆补体（C）/凝血/血管因子、病毒/微生物检测、脂溶性维生素和淋巴细胞计数；ii）复发期和缓解期时动态磁敏感对比增强 3T-MRI 的脑血液动力学指标；iii）多发性硬化症患者的实验室数据与 MRI 灌注指标和临床特征。我们使用两组数据进行了偏最小二乘判别分析（PLS-DA）的两个模型：（1）多发性硬化症 vs. 对照组；（2）复发型 vs. 缓解型多发性硬化症。
与对照组相比，多发性硬化症患者的体重指数、蛋白 C 和活化的 C9 更高，而活化的 C4 较低。组织因子、Tie-2 和 P-选择素/CD62P 在复发期低于缓解期和对照组，而血管生成素-I 在复发型多发性硬化症中高于缓解型多发性硬化症。复发型多发性硬化症的总淋巴细胞数低于缓解型多发性硬化症和对照组。正常表现的白质和左侧尾状核的脑血容量较低，而双侧壳核的脑血流较低。钆增强病变的平均转运时间与组织因子呈负相关。模型（1）中排名前 5 的区分变量为：EBV-EBNA-1 IgG、体重指数、蛋白 C、活化的 C4 和组织因子；而模型（2）中排名前 5 的变量为：组织因子、血管生成素-I、MCHC、维生素 A 和 T-CD3。
组织因子是区分多发性硬化症与对照组或多发性硬化症复发与缓解的前 5 个变量之一，与钆增强病变的平均转运时间相关。组织因子似乎是一种有前途的促凝/血管生物标志物，也是复发性缓解型多发性硬化症的潜在治疗靶点。
ClinicalTrials.gov，标识符 NCT04380220。
