血清神经丝轻链水平可预测进行性多发性硬化症患者的长期残疾进展。

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis.

作者信息

Comabella Manuel, Sastre-Garriga Jaume, Carbonell-Mirabent Pere, Fissolo Nicolás, Tur Carmen, Malhotra Sunny, Pareto Deborah, Aymerich Francesc X, Río Jordi, Rovira Alex, Tintoré Mar, Montalban Xavier

机构信息

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

出版信息

J Neurol Neurosurg Psychiatry. 2022 Apr 29. doi: 10.1136/jnnp-2022-329020.

DOI:10.1136/jnnp-2022-329020

PMID:35487685

Abstract

UNLABELLED

ObjectiveThere is a lack of sensitive and specific biomarkers for use in progressive multiple sclerosis (MS). The study aimed to assess the potential of serum neurofilament light chain (sNfL) levels as biomarker of disability progression in patients with progressive MS.

METHODS

We performed a prospective observational cohort study in 51 patients with progressive MS who participated in a 2-year phase II single-centre, randomised, double-blind, placebo-controlled trial of interferon-beta. Mean (SD) follow-up duration was 13.9 (6.2) years. Levels of sNfL were measured using a single molecule array immunoassay at baseline, 1, 2 and 6 years. Univariable and multivariable analyses were carried out to evaluate associations between sNfL levels and disability progression at short term (2 years), medium term (6 years) and long term (at the time of the last follow-up).

RESULTS

A sNfL cut-off value of 10.2 pg/mL at baseline discriminated between long-term progressors and non-progressors with a 75% sensitivity and 67% specificity (adjusted OR 7.8; 95% CI 1.8 to 46.4; p=0.01). Similar performance to discriminate between long-term progressors and non-progressors was observed using age/body mass index-adjusted sNfL Z-scores derived from a normative database of healthy controls. A cut-off increase of 5.1 pg/mL in sNfL levels between baseline and 6 years also discriminated between long-term progressors and non-progressors with a 71% sensitivity and 86% specificity (adjusted OR 49.4; 95% CI 4.4 to 2×10; p=0.008).

CONCLUSIONS

sNfL can be considered a prognostic biomarker of future long-term disability progression in patients with progressive MS. These data expand the little knowledge existing on the role of sNfL as long-term prognostic biomarker in patients with progressive MS.

摘要

未标注

目的

用于进行性多发性硬化症（MS）的敏感且特异的生物标志物缺乏。本研究旨在评估血清神经丝轻链（sNfL）水平作为进行性MS患者残疾进展生物标志物的潜力。

方法

我们对51例进行性MS患者进行了一项前瞻性观察队列研究，这些患者参与了一项为期2年的II期单中心、随机、双盲、安慰剂对照的干扰素-β试验。平均（标准差）随访时间为13.9（6.2）年。在基线、1年、2年和6年时，使用单分子阵列免疫测定法测量sNfL水平。进行单变量和多变量分析，以评估sNfL水平与短期（2年）、中期（6年）和长期（最后一次随访时）残疾进展之间的关联。

结果

基线时sNfL临界值为10.2 pg/mL，可区分长期进展者和非进展者，敏感性为75%，特异性为67%（校正比值比7.8；95%置信区间1.8至46.4；p=0.01）。使用从健康对照的标准数据库得出的年龄/体重指数校正的sNfL Z分数，观察到在区分长期进展者和非进展者方面有类似的表现。基线至6年期间sNfL水平截断值增加5.1 pg/mL，也可区分长期进展者和非进展者，敏感性为71%，特异性为86%（校正比值比49.4；95%置信区间4.4至2×10；p=0.008）。