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那他珠单抗治疗多发性硬化症患者的临床免疫学相关性

Clinical Immunological Correlations in Patients with Multiple Sclerosis Treated with Natalizumab.

作者信息

Maier Smaranda, Simu Mihaela, Hutanu Adina, Barcutean Laura, Voidazan Septimiu, Bajko Zoltan, Motataianu Anca, Lata Irina, Balasa Rodica

机构信息

Neurology 1 Clinic, Emergency Clinical County Hospital Mures, 540136 Targu Mures, Romania.

Neurology Department, University of Medicine, Pharmacy, Science and Technology, "G. E. Palade", 540139 Targu Mures, Romania.

出版信息

Brain Sci. 2020 Oct 30;10(11):802. doi: 10.3390/brainsci10110802.

Abstract

Natalizumab (NAT) was the first disease modifying therapy used for the treatment of relapsing-remitting multiple sclerosis (MS) that was designed with a specific mechanism of action that targets an important step of the MS immunopathology, directly blocking the T lymphocyte intrusion in the central nervous system. Initially, it was considered that NAT carried no biological effects on the peripheral immune response. The purpose of our study was to assess the effects of NAT on the peripheral pro and anti-inflammatory cytokines and to reveal possible correlations between them and the clinical activity of the disease. We noticed a significant decrease in interleukin (IL)-17, tumor necrosis factor-alpha (TNF-α) and IL-31 serum levels in treated patients. The lack of relapses during the study was associated with low baseline IL-17 level. The patients that had an increase in the disability score during the study had significantly lower IL-17 and higher IL-1β baseline levels. IL-17 can be used as a biomarker for disease activity but also for progression assessment in NAT treated patients. NAT has a far more complex mechanism compared to what was initially believed, besides modulating lymphocyte trafficking through the blood-brain barrier, it also changes the peripheral levels of pro and anti-inflammatory cytokines in MS patients.

摘要

那他珠单抗(NAT)是首个用于治疗复发缓解型多发性硬化症(MS)的疾病修正疗法,其设计具有特定作用机制,针对MS免疫病理学的一个重要步骤,直接阻断T淋巴细胞侵入中枢神经系统。最初,人们认为NAT对外周免疫反应没有生物学效应。我们研究的目的是评估NAT对外周促炎和抗炎细胞因子的影响,并揭示它们与疾病临床活动之间可能存在的相关性。我们注意到,接受治疗的患者血清白细胞介素(IL)-17、肿瘤坏死因子-α(TNF-α)和IL-31水平显著降低。研究期间无复发与低基线IL-17水平相关。研究期间残疾评分增加的患者IL-17基线水平显著更低,而IL-1β基线水平更高。IL-17可作为疾病活动的生物标志物,也可用于评估接受NAT治疗患者的病情进展。与最初认为的情况相比,NAT的机制要复杂得多,除了调节淋巴细胞通过血脑屏障的运输外,它还会改变MS患者外周促炎和抗炎细胞因子的水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f137/7692182/f7023b805e22/brainsci-10-00802-g001.jpg

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