Brigham and Women's Hospital, Boston, MA, USA.
Octave Bioscience, Inc, Menlo Park, CA, USA.
Nat Commun. 2024 May 20;15(1):4297. doi: 10.1038/s41467-024-48602-9.
The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.
多发性硬化症的多面性需要定量生物标志物，这些标志物可以提供与多种生理途径相关的见解。为此，对深度表型血清样本进行蛋白质组学分析、生物途径建模和网络分析，以阐明炎症和神经退行性过程，确定多发性硬化症疾病活动的敏感生物标志物。在这里，我们评估了来自三个多发性硬化症队列的 630 个样本中 > 1400 种血清蛋白的浓度，以确定与临床和影像学新发疾病活动的关联。20 种蛋白与临床和影像学多发性硬化症疾病活动的增加相关，被纳入定制检测面板。血清神经丝轻链与钆增强病变活动、临床复发状态和年复发率的相关性最强。所有终点的多变量模型均优于单变量模型。包含本研究中确定的 20 种蛋白的综合生物标志物面板可用于表征多发性硬化症患者的疾病活动。
