Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Octave Bioscience, Menlo Park, CA, USA.
J Neurol Sci. 2024 Jun 15;461:123055. doi: 10.1016/j.jns.2024.123055. Epub 2024 May 14.
Atrophied lesion volume (aLV), a proposed biomarker of disability progression in multiple sclerosis (MS) and transition into progressive MS (PMS), depicts chronic periventricular white matter (WM) pathology. Meningeal infiltrates, imaged as leptomeningeal contrast enhancement (LMCE), are linked with greater cortical pathology.
To determine the relationship between serum-derived proteomic data with the development of aLV and LMCE in a heterogeneous group of people with MS (pwMS).
Proteomic and MRI data for 202 pwMS (148 clinically isolated syndrome /relapsing-remitting MS and 54 progressive MS (PMS)) were acquired at baseline and at 5.4-year follow-up. The concentrations of 21 proteins related to multiple MS pathophysiology pathways were derived using a custom-developed Proximity Extension Assay on the Olink™ platform. The accrual of aLV was determined as the volume of baseline T2-weighted lesions that were replaced by cerebrospinal fluid over the follow-up. Regression models and age-adjusted analysis of covariance (ANCOVA) were used.
Older age (standardized beta = 0.176, p = 0.022), higher glial fibrillary acidic protein (standardized beta = 0.312, p = 0.001), and lower myelin oligodendrocyte glycoprotein levels (standardized beta = -0.271, p = 0.002) were associated with accrual of aLV over follow-up. This relationship was driven by the pwPMS population. The presence of LMCE at the follow-up visit was not predicted by any baseline proteomic biomarker nor cross-sectionally associated with any protein concentration.
Proteomic markers of glial activation are associated with chronic lesional WM pathology (measured as aLV) and may be specific to the progressive MS phenotype. LMCE presence in MS does not appear to relate to proteomic measures.
萎缩性病变体积（aLV）是多发性硬化症（MS）残疾进展和向进展性多发性硬化症（PMS）转变的一个潜在生物标志物，描述了慢性脑室周围白质（WM）病理学。脑膜浸润，作为软脑膜对比增强（LMCE）成像，与更大的皮质病理学有关。
确定血清衍生蛋白质组数据与一组异质性 MS 患者（pwMS）中 aLV 和 LMCE 发展之间的关系。
在基线和 5.4 年随访时，获取了 202 名 pwMS（148 例临床孤立综合征/复发缓解型 MS 和 54 例进展型 MS（PMS））的蛋白质组学和 MRI 数据。使用定制的邻近延伸测定法（Olink 平台）从 21 种与多种 MS 病理生理学途径相关的蛋白质中提取浓度。aLV 的累积量是通过对随访过程中用脑脊液取代的基线 T2 加权病变的体积来确定的。使用回归模型和年龄调整协方差分析（ANCOVA）进行分析。
年龄较大（标准化β=0.176，p=0.022）、胶质纤维酸性蛋白较高（标准化β=0.312，p=0.001）和少突胶质细胞髓鞘糖蛋白水平较低（标准化β=-0.271，p=0.002）与随访期间 aLV 的累积量有关。这种关系是由 pwPMS 人群驱动的。在随访时存在 LMCE 既不受任何基线蛋白质组生物标志物预测，也与任何蛋白质浓度没有横断面关联。
胶质激活的蛋白质组学标志物与慢性病变性 WM 病理学（以 aLV 衡量）相关，可能是进展性 MS 表型的特异性标志物。MS 中 LMCE 的存在似乎与蛋白质组学测量无关。
