Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.
Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.
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DOI：
10.1212/wnl.0000000000001642
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发表时间：
2015-06-02
期刊：
影响因子：
9.9
通讯作者：
Malaspina A
中科院分区：
文献类型：
--
作者：
Lu CH;Macdonald-Wallis C;Gray E;Pearce N;Petzold A;Norgren N;Giovannoni G;Fratta P;Sidle K;Fish M;Orrell R;Howard R;Talbot K;Greensmith L;Kuhle J;Turner MR;Malaspina A
检测肌萎缩性侧索硬化症（ALS）患者血液和脑脊液神经丝轻链（NfL）水平与疾病进展和生存的关系。使用电化学发光免疫分析法，在伦敦（ALS/对照，血浆：n = 103/42）和牛津（ALS/对照，血清：n = 64/36；配对CSF: n = 38/20）招募的2组散发性ALS患者和健康对照样本中测量NfL水平。在长达3年的时间间隔内定期测量患者的NfL水平。ALS功能评定量表的变化-采用修订后的评分来评估疾病进展。生存率采用Cox回归和Kaplan-Meier分析。CSF、血清和血浆NfL区分ALS患者与健康对照具有高敏感性（分别为97%、89%、90%）和特异性（分别为95%、75%、71%）。脑脊液NfL与血清水平高度相关（r = 0.78, p < 0.0001）。在这两个队列中，ALS患者血液中NfL水平大约是对照组的4倍，并且在随访期间保持相对稳定的表达。招募时血液NfL水平是强有力的、独立的生存预测指标。基线时血NfL的最高分位数死亡率风险比为3.91（95%可信区间1.98 ~ 7.94,p < 0.001）。血源性NfL水平是一种易于获得的具有ALS预后价值的生物标志物。单个相对稳定的纵向水平为NfL作为未来治疗试验的药效学生物标志物提供了潜力。本报告提供了III级证据，证明NfL电化学发光免疫分析法能够准确区分散发性ALS患者和健康对照。
To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale–Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan–Meier analysis. CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98–7.94, p < 0.001). Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.