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多发性硬化症患者从注射治疗改为芬戈莫德后血浆神经丝轻链水平。

Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod.

机构信息

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden/Department of Neurology, Karolinska University Hospital Solna, Stockholm, Sweden.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden/Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

出版信息

Mult Scler. 2018 Jul;24(8):1046-1054. doi: 10.1177/1352458517715132. Epub 2017 Jun 19.

DOI:10.1177/1352458517715132
PMID:28627962
Abstract

BACKGROUND

Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS).

OBJECTIVE

To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod.

METHODS

A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL).

RESULTS

Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n  = 66, rho  = 0.672, p  < 0.0001 and n  = 16, rho  = 0.684, p  = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10), and levels remained stable at 24 months (13.2 (6.2)).

CONCLUSION

NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.

摘要

背景

神经丝轻链(NFL)是多发性硬化症(MS)中神经轴突损伤的脑脊液(CSF)标志物。

目的

确定 CSF 和血清/血浆中 NFL 的相关性,以及从注射性 MS 治疗转换为芬戈莫德后血浆中的 NFL 相关性。

方法

第一队列由 MS 患者(n=39)和神经疾病对照组(n=27)组成,他们的 CSF 和血浆/血清是为诊断目的而收集的。第二队列(n=243)由芬戈莫德上市后研究的患者组成。使用单分子阵列(Simoa™)技术(检测下限 1.95pg/mL)来确定 NFL。

结果

对照组和 MS 患者 CSF 中的 NFL pg/mL(平均值(标准差))分别为 341(267)和 1475(2358),血清中的 NFL pg/mL 分别为 8.2(3.58)和 17.0(16.94)。CSF/血清和血浆/血清水平高度相关(n=66,rho=0.672,p<0.0001,n=16,rho=0.684,p=0.009)。在开始使用芬戈莫德的患者中(n=243),血浆中的 NFL pg/mL(平均值(标准差))在基线时为 20.4(10.7),在 12 个月时为 13.5(7.3)(p<3×10),在 24 个月时保持稳定(13.2(6.2))。

结论

血清和 CSF 中的 NFL 高度相关,转换为高效 MS 治疗后,血浆 NFL 水平下降。血液 NFL 测量可被视为 MS 治疗反应的生物标志物。

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