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, Vall d'Hebron University Hospital, Barcelona, Spain.
Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
J Neurol Neurosurg Psychiatry. 2024 Apr 12;95(5):410-418. doi: 10.1136/jnnp-2023-332251.
We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).
A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.
Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.
Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.
我们旨在研究血清生物标志物水平在多中心真实世界原发性进展型多发性硬化症（PPMS）患者队列中预测残疾进展的潜力。
共纳入来自 18 个欧洲 MS 中心的 141 名 PPMS 患者。使用扩展残疾状况量表（EDSS）评分的变化来研究残疾进展，该评分在三个时间间隔内进行评估：基线至 2 年、6 年和最后一次随访。使用单分子阵列分析在基线时测量神经丝轻链（sNfL）、神经胶质纤维酸性蛋白（sGFAP）和几丁质酶 3 样蛋白 1（sCHI3L1）的血清水平。使用 Spearman's r 量化生物标志物水平之间以及生物标志物与年龄之间的相关性。使用单变量和多变量线性模型评估生物标志物水平与不同时间段 EDSS 变化之间的关联。
患者的中位（IQR）年龄为 52.9（46.4-58.5）岁，58 名（41.1%）为男性。中位随访时间为 9.1（7.0-12.6）年。仅 8 名（5.7%）患者在随访期间接受了治疗。sNfL 和 sGFAP 水平中度相关（r=0.43），与 sCHI3L1 水平均弱相关（r=0.19 和 r=0.17）。在多变量分析中，三种生物标志物的水平与所有时间段的 EDSS 变化相关。然而，当根据临床和影像学参数（n=64）将分析限制在非炎症患者时，只有 sCHI3L1 水平与未来 EDSS 变化相关。
sNfL、sGFAP 和 sCHI3L1 水平是与 PPMS 患者残疾进展相关的预后生物标志物，而 CHI3L1 发现较少依赖于与疾病进展相关的炎症成分。
