PDF(Pubmed)
Abstract：
Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.
摘要：
多发性硬化症（MS）和抗体介导的中枢神经系统疾病（CNS）患者的合并症，包括视神经脊髓炎谱系障碍（NMOSD），和髓鞘少突胶质细胞糖蛋白（MOG）-抗体相关疾病（MOGAD）很常见，可能会影响其神经系统疾病的进程。合并症可能导致神经元损伤，因此限制了从攻击中恢复。加速疾病进展,增加残疾。本研究旨在探讨共病的影响，特别是血管合并症，及相关危险因素对MS临床和临床参数的影响，NMOSD和MOGAD。我们建议COMMIT，一项前瞻性多中心研究，对MS患者进行纵向随访，NMOSD,和MOGAD,有或没有合并症，以及健康受试者作为对照。受试者将按年龄分层，性别和种族。在连续样品中，我们将使用多种最先进的技术分析外周血和脑脊液（CSF）的液体和细胞区室中的炎症和神经变性标志物水平，包括非靶向蛋白质组学和靶向超灵敏ELISA测定和定量逆转录聚合酶链反应（RT-qPCR）以及高维单细胞技术，即质谱和单细胞RNA测序。基于算法的数据分析将用于解开这些标记之间的关系，光学相干断层扫描（OCT）和磁共振成像（MRI），和临床结果，包括复发的频率和严重程度，长期残疾,和生活质量。目标是评估合并症对MS的影响，NMOSD,和MOGAD，这可能导致治疗方法的发展，以改善中枢神经系统的炎性脱髓鞘疾病的结果。
