A comparative study of CSF neurofilament light and heavy chain protein in MS
A comparative study of CSF neurofilament light and heavy chain protein in MS
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DOI：
10.1177/1352458513482374
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Kappos, Ludwig
中科院分区：
文献类型：
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作者：
Kuhle, Jens;Plattner, Kim;Kappos, Ludwig
背景：缺乏可靠的轴突变性生物标志物。神经丝是完成这项任务的有希望的候选者。我们比较了两种高灵敏度测定法来测量神经丝蛋白的两个亚基（神经丝轻链 (NfL) 和神经丝重链 (NfH)）。方法：我们评估了 UmanDiagnostics NF-light((R)) 酶联免疫吸附测定 (ELISA) 在一组 148 名临床孤立综合征 (CIS) 或多发性患者的脑脊液 (CSF) 中的分析和临床性能。硬化症 (MS) 和 72 名对照。我们将我们的结果与我们之前开发的 CSF NfH(SMI35) 测定的参考水平进行了比较。结果：暴露于室温（最多 8 天）或重复解冻（最多 4 次解冻）不会影响 NfL 浓度的测量。与对照组相比，CIS/MS 所有疾病阶段的 NfL 值均较高 (p < 0.001)。 NfL 水平与疾病复发患者的扩展残疾状态量表 (EDSS) 评分（r(s) = 0.31；p = 0.002）、脊髓复发以及急性炎症的脑脊液标志物相关。在 CIS 患者 (p = 0.001) 和所有 MS 分期分组 (p = 0.035) 中，NfL 区分患者和对照的能力均大于 NfH(SMI35)。结论：NfL 被证明是一种稳定的蛋白质，是可靠生物标志物的重要先决条件，并且与ECL-NfH(SMI35)免疫测定。我们确认并扩展了之前关于神经丝作为神经退行性变的定量标记物的发现。我们的结果进一步支持神经丝作为多发性硬化症研究中神经保护治疗的潜在替代措施的作用。
Background: There is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)).Methods: We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light((R)) enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfH(SMI35) assay.Results: Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls (p 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease (r(s) = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfH(SMI35) in both CIS patients (p = 0.001) and all MS stages grouped together (p = 0.035).Conclusions: NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light((R)) ELISA performed better in discriminating patients from controls, compared with the ECL-NfH(SMI35) immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.