MS Center, Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307, Dresden, Germany.
Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
J Mol Med (Berl). 2019 Sep;97(9):1263-1271. doi: 10.1007/s00109-019-01812-x. Epub 2019 Jun 26.
Fingolimod (FTY) is known to have multiple effects on the immune system and the central nervous system (CNS) in patients with multiple sclerosis (MS). In this study, we evaluated the immunological and neurobiological effects of FTY in MS. Blood and cerebrospinal fluid (CSF) samples were collected from 15 MS patients before first FTY administration and after 4 months of FTY therapy. Immunophenotyping and evaluation of sphingosine-1-phosphate (S1P), neurofilament light chain (NFL), S-100 and neuron-specific enolase (NSE) levels were conducted. After 4 months of FTY therapy, absolute cell count in CSF was decreased from 6.33 to 2.43 MPt/l, accompanied by decreases of CD3+ (2.22 to 0.65 MPt/l) and of CD4+ counts (1.60 to 0.39 MPt/l). In blood, CD3+ (1.05 to 0.09 GPt/l), CD4+ (0.80 to 0.02 GPt/l), CD8+ (0.23 to 0.04 GPt/l) and CD19+ (0.21 to 0.01GPt/l) cell counts were as well reduced. CD14+ cell count remained stable over the same period (0.24 to 0.26GPt/l). NFL and S1P levels in CSF and blood were reduced over time (NFL: CSF 1759 to 1359 pg/l, blood 8.42 to 7.36 pg/l; S1P: CSF 2.12 to 0.71 nmol/l, blood 392.1 to 312.9 nmol/l). Strong correlations between CSF and blood NFL levels were observed. Neuronal damage markers such as S-100 (1.86 to 1.69 μg/l) and NSE (9.53 to 8.67 μg/l) were reduced to a lesser degree than other markers. FTY exerted significant effects on immunological and neurobiological markers in the central and peripheral compartment. Decreases in levels of neuroinflammatory and neurodegenerative markers were already evident after 4 months of treatment. Four-month serum NFL level appears to be a useful marker for FTY efficacy that correlates well with changes in the CNS compartment. KEY MESSAGES: FTY has important immunological effects in both central and peripheral compartments. Cellular effects of FTY effects are more pronounced in the blood than in the CSF. FTY reduces S1P and NFL levels in CSF and serum. Serum NFL appears to be a useful marker for FTY therapy.
芬戈莫德（FTY）已知对多发性硬化症（MS）患者的免疫系统和中枢神经系统（CNS）具有多种作用。在这项研究中，我们评估了 FTY 在 MS 中的免疫学和神经生物学作用。在首次接受 FTY 治疗前和 FTY 治疗 4 个月后，从 15 名 MS 患者中采集了血液和脑脊液（CSF）样本。进行了免疫表型分析和神经鞘氨醇-1-磷酸（S1P）、神经丝轻链（NFL）、S-100 和神经元特异性烯醇化酶（NSE）水平的评估。在接受 FTY 治疗 4 个月后，CSF 中的绝对细胞计数从 6.33 减少到 2.43 MPt/l，同时 CD3+（从 2.22 减少到 0.65 MPt/l）和 CD4+计数减少（从 1.60 减少到 0.39 MPt/l）。在血液中，CD3+（从 1.05 减少到 0.09 GPt/l）、CD4+（从 0.80 减少到 0.02 GPt/l）、CD8+（从 0.23 减少到 0.04 GPt/l）和 CD19+（从 0.21 减少到 0.01 GPt/l）细胞计数也减少了。同期 CD14+细胞计数保持稳定（0.24 至 0.26 GPt/l）。CSF 和血液中的 NFL 和 S1P 水平随时间减少（NFL：CSF 1759 至 1359 pg/l，血液 8.42 至 7.36 pg/l；S1P：CSF 2.12 至 0.71 nmol/l，血液 392.1 至 312.9 nmol/l）。观察到 CSF 和血液 NFL 水平之间存在很强的相关性。神经元损伤标志物，如 S-100（从 1.86 减少到 1.69 μg/l）和 NSE（从 9.53 减少到 8.67 μg/l），比其他标志物减少的程度要小。FTY 对中枢和外周隔室的免疫和神经生物学标志物均有显著影响。在治疗 4 个月后，神经炎症和神经退行性标志物的水平已经降低。4 个月时的血清 NFL 水平似乎是 FTY 疗效的一个有用标志物，与中枢神经系统隔室的变化密切相关。关键信息：FTY 在中枢和外周隔室均具有重要的免疫作用。FTY 的细胞作用在血液中比在 CSF 中更为明显。FTY 降低 CSF 和血清中的 S1P 和 NFL 水平。血清 NFL 似乎是 FTY 治疗的一个有用标志物。
