Background The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared. Methods During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively. Results Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman’s rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF. Conclusion A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.

中文翻译：

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位置很重要：在利妥昔单抗治疗进展性 MS 的临床试验中，来自不同 CNS 区室的样本中蛋白质水平高度不同

背景 不同 CNS 细胞外区室中蛋白质之间的关系尚不清楚。在这项研究中，比较了进行性多发性硬化症 (PMS) 患者三个隔室中选定蛋白质的水平。方法 在一项关于利妥昔单抗脑室内给药治疗 PMS 的开放标签、1b 期研究期间，通过微透析从大脑的间隙空间 (ISS) 收集样本。还从心室和腰部脑脊液 (CSF) 中获取样品。使用多重邻近延伸测定法分析这些样品，测量在两个面板之间平均分配的 180 种蛋白质的水平，分别检测与免疫学和神经学相关的蛋白质。结果 在三个分析的隔室之间观察到了相当大的浓度差异。与心室 CSF 相比，ISS 流体含有显着更高水平的 25 种蛋白质（84% 免疫学组和 16% 神经学组）。与 ISS 液体相比，心室 CSF 含有显着更高水平的 54 种蛋白质（31% 免疫学组和 69% 神经学组），与腰椎 CSF 相比，17 种蛋白质（76% 免疫学组和 24% 神经学组）含有显着更高水平。与心室 CSF 相比，腰椎 CSF 显示出显着更高水平的 115 种蛋白质（32% 免疫学组和 68% 神经学组）。这三个隔室与 ISS 和心室 CSF 之间的 Spearman's rho 中值 -0.1 (IQR 0.4) 和心室和腰椎 CSF 之间的中值 Spearman's rho 相关性较差，相关性为 0.3 (IQR 0.4)。结论 可见从不同 CNS 区室获得的样品的蛋白质水平存在显着异质性。所以，