Chitnis Tanuja, Qureshi Ferhan, Gehman Victor M, Becich Michael, Bove Riley, Cree Bruce A C, Gomez Refujia, Hauser Stephen L, Henry Roland G, Katrib Amal, Lokhande Hrishikesh, Paul Anu, Caillier Stacy J, Santaniello Adam, Sattarnezhad Neda, Saxena Shrishti, Weiner Howard, Yano Hajime, Baranzini Sergio E
medRxiv. 2023 Jul 3:2023.06.28.23291157. doi: 10.1101/2023.06.28.23291157.
BACKGROUND/OBJECTIVES: Serum proteomic analysis of deeply-phenotyped samples, biological pathway modeling and network analysis were performed to elucidate the inflammatory and neurodegenerative processes of multiple sclerosis (MS) and identify sensitive biomarkers of MS disease activity (DA).
Over 1100 serum proteins were evaluated in >600 samples from three MS cohorts to identify biomarkers of clinical and radiographic (gadolinium-enhancing lesions) new MS DA. Protein levels were analyzed and associated with presence of gadolinium-enhancing lesions, clinical relapse status (CRS), and annualized relapse rate (ARR) to create a custom assay panel.
Twenty proteins were associated with increased clinical and radiographic MS DA. Serum neurofilament light chain (NfL) showed the strongest univariate correlation with radiographic and clinical DA measures. Multivariate modeling significantly outperformed univariate NfL to predict gadolinium lesion activity, CRS and ARR.
These findings provide insight regarding correlations between inflammatory and neurodegenerative biomarkers and clinical and radiographic MS DA.
Octave Bioscience, Inc (Menlo Park, CA).
背景/目的：对深度表型样本进行血清蛋白质组分析、生物通路建模和网络分析，以阐明多发性硬化症（MS）的炎症和神经退行性变过程，并识别MS疾病活动（DA）的敏感生物标志物。
在来自三个MS队列的600多个样本中评估了1100多种血清蛋白，以识别临床和影像学（钆增强病灶）新发MS DA的生物标志物。分析蛋白水平，并将其与钆增强病灶的存在、临床复发状态（CRS）和年化复发率（ARR）相关联，以创建一个定制检测面板。
20种蛋白与临床和影像学MS DA增加相关。血清神经丝轻链（NfL）与影像学和临床DA指标的单变量相关性最强。多变量建模在预测钆病灶活动、CRS和ARR方面显著优于单变量NfL。
这些发现为炎症和神经退行性生物标志物与临床和影像学MS DA之间的相关性提供了见解。
奥克塔夫生物科学公司（加利福尼亚州门洛帕克）
