Quantifying cell subpopulations in biological fluids aids in diagnosis and understanding of the mechanisms of injury. Although much has been learned from cerebrospinal fluid (CSF) flow cytometry in neuroimmunological disorders such as multiple sclerosis (MS), previous studies did not contain enough healthy donors (HD) to derive age- and gender-related normative data and sufficient heterogeneity of other inflammatory neurological diseases (OIND) controls to identify MS specific changes. The goals of this blinded, training and validation study of MS patients and embedded controls, representing 1240 prospectively-acquired paired CSF/blood samples from 588 subjects was: 1. To define physiological age/gender-related changes in CSF cells; 2. To define/validate cellular abnormalities in blood and CSF of untreated MS through disease duration (DD) and determine which are MS-specific; 3. To compare effect(s) of low-efficacy (i.e., interferon-beta [IFN-beta] and glatiramer acetate [GA]) and high-efficacy drugs (i.e., natalizumab, daclizumab and ocrelizumab) on MS-related cellular abnormalities using propensity score matching. Physiological gender differences are less pronounced in the CSF compared to blood, while age-related changes suggest decreased immunosurveillance of CNS by activated, HLA-DR+ T cells associated with natural aging. Results from patient samples support concept of MS being immunologically single disease evolving in time. Initially, peripherally activated innate and adaptive immune cells migrate into CSF to form MS lesions. With progression, T cells (CD8+ > CD4+), NK cells and myeloid dendritic cells are depleted from blood as they continue to accumulate, together with B cells, in the CSF and migrate to CNS tissue forming compartmentalized inflammation. All MS drugs inhibit non-physiological accumulation of immune cells in the CSF. While low efficacy drugs tend to normalize it, high efficacy drugs overshoot some aspects of CSF physiology suggesting impairment of CNS immunosurveillance. Comparable inhibition of MS-related CSF abnormalities advocates changes within CNS parenchyma responsible for differences in drug's efficacy on MS disability progression. Video summarizing all results may become useful educational tool.

中文翻译：

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广泛的健康捐赠者年龄/性别调整和倾向得分匹配通过免疫表型揭示多发性硬化症的生理学

定量生物液中的细胞亚群有助于诊断和了解损伤机制。尽管从脑脊髓液（CSF）流式细胞术学到的神经免疫性疾病（例如多发性硬化症（MS））学到了很多东西，但以前的研究并没有足够的健康捐献者（HD）来获得与年龄和性别相关的规范性数据，而其他研究也没有足够的异质性炎症性神经疾病（OIND）控件可识别MS的特定变化。这项针对588名受试者的1240例预期获得的配对CSF /血液样本的MS患者和嵌入式对照的盲目，训练和验证研究的目标是：1.定义CSF细胞的生理年龄/性别相关变化；2。通过疾病持续时间（DD）定义/验证未经治疗的MS的血液和脑脊液中的细胞异常，并确定哪些是MS特异性的；3.比较低效（即干扰素-β[IFN-β]和醋酸格拉替雷[GA]）和高效药（即那他珠单抗，达克珠单抗和奥克珠单抗）对MS相关细胞异常的作用使用倾向得分匹配。与血液相比，CSF中的生理性别差异不太明显，而与年龄相关的变化表明与自然衰老相关的活化的HLA-DR + T细胞对CNS的免疫监视降低。患者样本的结果支持了MS是随着时间发展的免疫性单一疾病的概念。最初，外周活化的先天和适应性免疫细胞迁移到CSF中形成MS病变。随着进展，T细胞（CD8 +> CD4 +），随着NK细胞和骨髓树突状细胞与B细胞一起继续积聚在CSF中，它们从血液中耗尽，并迁移到CNS组织，形成间隔性炎症。所有MS药物均会抑制CSF中免疫细胞的非生理积累。低效药物倾向于使其正常化，而高效药物则超过了CSF生理学的某些方面，提示中枢神经系统免疫监视受损。与MS相关的CSF异常的类似抑制作用提倡中枢神经系统实质内的变化，这导致药物对MS残疾进展的功效差异。总结所有结果的视频可能会成为有用的教育工具。所有MS药物均会抑制CSF中免疫细胞的非生理积累。低效药物倾向于使其正常化，而高效药物则超出了CSF生理学的某些方面，表明中枢神经系统免疫监视功能受损。与MS相关的CSF异常的类似抑制作用提倡中枢神经系统实质内的变化，这导致药物对MS残疾进展的功效差异。总结所有结果的视频可能会成为有用的教育工具。所有MS药物均会抑制CSF中免疫细胞的非生理积累。低效药物倾向于使其正常化，而高效药物则超出了CSF生理学的某些方面，表明中枢神经系统免疫监视功能受损。与MS相关的CSF异常的类似抑制作用提倡中枢神经系统实质内的变化，这导致药物对MS残疾进展的功效差异。总结所有结果的视频可能会成为有用的教育工具。对MS残疾进展的疗效。总结所有结果的视频可能会成为有用的教育工具。对MS残疾进展的疗效。总结所有结果的视频可能会成为有用的教育工具。