Neurofilament light chain level is a weak risk factor for the development of MS.
Neurofilament light chain level is a weak risk factor for the development of MS.
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DOI：
10.1212/wnl.0000000000003085
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发表时间：
2016-09-13
期刊：
影响因子：
9.9
通讯作者：
Tintore M
中科院分区：
文献类型：
--
作者：
Arrambide G;Espejo C;Eixarch H;Villar LM;Alvarez-Cermeño JC;Picón C;Kuhle J;Disanto G;Kappos L;Sastre-Garriga J;Pareto D;Simon E;Comabella M;Río J;Nos C;Tur C;Castilló J;Vidal-Jordana A;Galán I;Arévalo MJ;Auger C;Rovira A;Montalban X;Tintore M
确定选定的生物标志物在临床孤立综合征（CIS）转化为多发性硬化症（MS）和残疾累积中的预后价值。数据来自2个CIS队列。筛选阶段评估临床明确的多发性硬化症（CIS- cdms）患者和在2年最低随访期间（CIS-CIS）仍为多发性硬化症的患者。我们测定了脑脊液中神经束蛋白、信号蛋白3A、胎儿素A、胶质纤维酸性蛋白、神经丝轻链（NfL）和重链的水平（估计平均值[95%置信区间；CI]）。我们评估了生物标志物水平、转化、残疾和磁共振参数之间的关系。在复制阶段，我们使用900 ng/L的临界值来测定NfL水平（n = 155）。单因素和多因素分析的主要终点是CDMS和2010 McDonald ms。筛选中唯一显示显著差异的生物标志物是NfL （CIS-CDMS 1,553.1 [1,208.7-1,897.5] ng/L和CIS-CIS 499.0 [168.8-829.2] ng/L, p < 0.0001）。与5岁时脑实质分数变化（rs = - 0.892）和脑体积变化百分比（rs = - 0.842）的相关性最强。NfL与残疾无关。在复制阶段，根据截止值，更多的NfL阳性患者进化为MS，每增加100 ng/L的NfL预测CDMS（风险比[HR] = 1.009, 95% CI 1.005 - 1.014）和McDonald MS (HR = 1.009, 95% CI 1.005 - 1.013)，在多变量分析中CDMS仍然具有显著性（校正HR = 1.005, 95% CI 1.000-1.011）。这种风险低于存在寡克隆带或T2病变。NfL是ms的一个较弱的独立危险因素，其作为轴突损伤生物标志物的作用可能与中期脑容量变化的相关性更大。
To determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual. Data were acquired from 2 CIS cohorts. The screening phase evaluated patients developing clinically definite MS (CIS-CDMS) and patients who remained as CIS during a 2-year minimum follow-up (CIS-CIS). We determined levels of neurofascin, semaphorin 3A, fetuin A, glial fibrillary acidic protein, and neurofilament light (NfL) and heavy chains in CSF (estimated mean [95% confidence interval; CI]). We evaluated associations between biomarker levels, conversion, disability, and magnetic resonance parameters. In the replication phase, we determined NfL levels (n = 155) using a 900 ng/L cutoff. Primary endpoints in uni- and multivariate analyses were CDMS and 2010 McDonald MS. The only biomarker showing significant differences in the screening was NfL (CIS-CDMS 1,553.1 [1,208.7–1,897.5] ng/L and CIS-CIS 499.0 [168.8–829.2] ng/L, p < 0.0001). The strongest associations were with brain parenchymal fraction change (rs = −0.892) and percentage brain volume change (rs = −0.842) at 5 years. NfL did not correlate with disability. In the replication phase, more NfL-positive patients, according to the cutoff, evolved to MS. Every 100-ng/L increase in NfL predicted CDMS (hazard ratio [HR] = 1.009, 95% CI 1.005–1.014) and McDonald MS (HR = 1.009, 95% CI 1.005–1.013), remaining significant for CDMS in the multivariate analysis (adjusted HR = 1.005, 95% CI 1.000–1.011). This risk was lower than the presence of oligoclonal bands or T2 lesions. NfL is a weak independent risk factor for MS. Its role as an axonal damage biomarker may be more relevant as suggested by its association with medium-term brain volume changes.