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血浆神经丝轻链和胶质纤维酸性蛋白与多发性硬化残疾恶化的关系。

Plasma glial fibrillary acidic protein and neurofilament light chain in relation to disability worsening in multiple sclerosis.

机构信息

Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium/Department of Neurology, Universitair Ziekenhuis Brussel, Jette, Belgium/Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium/VIB Center for Microbiology, Leuven, Belgium/National Multiple Sclerosis Center Melsbroek, Melsbroek, Belgium.

Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium/AIMS, Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium/ETRO, Vrije Universiteit Brussel, Elsene, Belgium.

出版信息

Mult Scler. 2022 Oct;28(11):1685-1696. doi: 10.1177/13524585221094224. Epub 2022 May 21.

Abstract

BACKGROUND

Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce.

OBJECTIVE

To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening.

METHODS

We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure.

RESULTS

In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 ± 0.82 years, while p-NfL (HR = 1.046,  = 0.001), EDSS (HR = 1.24,  = 0.039), and disease duration (HR = 1.048,  = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP ( = 0.031) and 0.63 for p-NfL ( = 0.015). Kaplan-Meier curves showed similar patterns for both proteins.

CONCLUSION

p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.

摘要

背景

预测多发性硬化症(MS)的残疾恶化仍然是一个重要的挑战。胶质纤维酸性蛋白(GFAP)和神经丝轻链(NfL)似乎是很有前途的生物标志物。研究表明,血液 GFAP 与 MS 的纵向结局指标有关,但此类研究很少。

目的

比较血浆 GFAP(p-GFAP)和血浆 NfL(p-NfL)水平与持续性残疾恶化的关系。

方法

我们使用单分子阵列(Simoa)测量了 115 名 MS 患者和 30 名匹配对照者的基线 p-GFAP 和 p-NfL。残疾恶化定义为至少有三种指标(扩展残疾状况量表、定时 25 英尺步行、9 孔钉测试)中的一项增加,经过 6 个月后得到确认,且在数据截止时仍然存在。

结果

在多变量 Cox 比例风险模型中,p-GFAP 与 4.40±0.82 年后的持续性残疾恶化无显著相关性,而 p-NfL(HR=1.046, = 0.001)、EDSS(HR=1.24, = 0.039)和疾病持续时间(HR=1.048, = 0.017)与之相关。p-GFAP 与恶化相关的 ROC 曲线下面积为 0.61( = 0.031),p-NfL 为 0.63( = 0.015)。ROC 曲线显示两种蛋白质的 Kaplan-Meier 曲线具有相似的模式。

结论

在 Cox 回归分析中,p-NfL 是恶化的显著解释变量,而 p-GFAP 不是。ROC 曲线显示,p-GFAP 和 p-NfL 均与恶化相关。

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