Atlas of Cerebrospinal Fluid Immune Cells Across Neurological Diseases

IF 8.1 1区 医学 Q1 CLINICAL NEUROLOGY
Michael Heming MD, Anna-Lena Börsch MSc, Simone Melnik MSc, Noemi Gmahl MD, Louisa Müller-Miny MD, Christine Dambietz MD, Lukas Fisch MSc, Timm Kühnel MSc, Tobias J. Brix PhD, Alice Janssen MSc, Eva Schumann MSc, Catharina C. Gross PhD, Julian Varghese MD, Tim Hahn PhD, Heinz Wiendl MD, Gerd Meyer zu Hörste MD
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引用次数: 0

Abstract

Objective

Cerebrospinal fluid (CSF) provides unique insights into the brain and neurological diseases. However, the potential of CSF flow cytometry applied on a large scale remains unknown.

Methods

We used data-driven approaches to analyze paired CSF and blood flow cytometry measurements from 8,790 patients (discovery cohort) and CSF only data from 3,201 patients (validation cohort) collected across neurological diseases in a real-world setting.

Results

In somatoform controls (n = 788), activation of T cells increased with age in both CSF and blood, whereas double negative blood T cells (CD3+CD4CD8) decreased with age. A machine learning model of CSF and blood immune cells defined immune age, which correlated strongly with true biological age (r = 0.71). Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative. This clustering was validated in an analytically independent test dataset (8,790 patients) and in a temporally independent cohort (3,201 patients). Patients with multiple sclerosis were more likely to have progressive disease when assigned to the neurodegeneration cluster and to have lower disability in the autoimmune cluster. Patients with dementia in the neurodegeneration cluster showed more severe disease progression. Flow cytometry helped differentiate dementia from controls, thereby enhancing the diagnostic power of routine CSF diagnostics.

Interpretation

Flow cytometry of CSF and blood thus identifies site-specific aging patterns and disease-overarching patterns of neurodegeneration. ANN NEUROL 2025;97:779–790

Abstract Image

神经系统疾病的脑脊液免疫细胞图谱。
目的:脑脊液(CSF)为大脑和神经系统疾病提供了独特的见解。然而,脑脊液流式细胞术大规模应用的潜力仍然未知。方法:我们使用数据驱动的方法来分析来自8,790例患者(发现队列)的配对CSF和血流式细胞术测量数据,以及来自3,201例患者(验证队列)的CSF数据,这些数据收集于真实世界的神经系统疾病中。结果:在躯体型对照(n = 788)中,脑脊液和血液中T细胞的激活随着年龄的增长而增加,而双阴性血T细胞(CD3+CD4-CD8-)随着年龄的增长而下降。脑脊液和血液免疫细胞的机器学习模型定义了免疫年龄,其与真实生物年龄密切相关(r = 0.71)。仅根据8,790例患者的脑脊液/血液参数对所有疾病进行分类,结果得出4种疾病类别:健康、自身免疫性、脑膜脑炎和神经退行性疾病。该聚类在分析独立的测试数据集(8,790例患者)和时间独立的队列(3,201例患者)中得到验证。当多发性硬化症患者被分配到神经退行性变性组时,更有可能出现进行性疾病,而在自身免疫性组中,残疾程度较低。神经退行性痴呆患者表现出更严重的疾病进展。流式细胞术有助于区分痴呆与对照组,从而提高常规脑脊液诊断的诊断能力。解释:脑脊液和血液的流式细胞术因此确定了特定部位的衰老模式和神经变性的疾病覆盖模式。Ann neurol 2024。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annals of Neurology
Annals of Neurology 医学-临床神经学
CiteScore
18.00
自引率
1.80%
发文量
270
审稿时长
3-8 weeks
期刊介绍: Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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