脑脊液质谱细胞术鉴定出与 MS 相关的 B 细胞群体。
Mass Cytometry of CSF Identifies an MS-Associated B-cell Population.
机构信息
From the Department of Biomedicine (D.J., J.R., E.G., I.C., M.D., J.K., T.D., N.S.R.S.), University Hospital Basel, University of Basel; Novartis Institutes for BioMedical Research (C. Rauld, C. Regairaz, L.R., A.W., R.C., G.R., J.M.C.); Swiss Institute of Bioinformatics (J.R.), Basel; Institute of Experimental Immunology (E.G., B.B.), University of Zurich; and Department of Medicine (E.G., M.D., J.K., T.D.), Neurologic Clinic and Policlinic, University Hospital and University of Basel, Switzerland.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2021 Feb 15;8(2). doi: 10.1212/NXI.0000000000000943. Print 2021 Mar.
OBJECTIVE
To identify an MS-specific immune cell population by deep immune phenotyping and relate it to soluble signaling molecules in CSF.
METHODS
We analyzed surface expression of 22 markers in paired blood/CSF samples from 39 patients using mass cytometry (cytometry by time of flight). We also measured the concentrations of 296 signaling molecules in CSF using proximity extension assay. Results were analyzed using highly automated unsupervised algorithmic informatics.
RESULTS
Mass cytometry objectively identified a B-cell population characterized by the expression of CD49d, CD69, CD27, CXCR3, and human leukocyte antigen (HLA)-DR as clearly associated with MS. Concentrations of the B cell-related factors, notably FCRL2, were increased in MS CSF, especially in early stages of the disease. The B-cell trophic factor B cell activating factor (BAFF) was decreased in MS. Proteins involved in neural plasticity were also reduced in MS.
CONCLUSION
When analyzed without a priori assumptions, both the soluble and the cellular compartments of the CSF in MS were characterized by markers related to B cells, and the strongest candidate for an MS-specific cell type has a B-cell phenotype.
目的
通过深度免疫表型分析识别多发性硬化症（MS）特异性免疫细胞群，并将其与 CSF 中的可溶性信号分子相关联。
方法
我们使用飞行时间质谱细胞仪（mass cytometry）分析了 39 名患者配对的血液/CSF 样本中 22 个标记物的表面表达。我们还使用邻近延伸分析（proximity extension assay）测量了 CSF 中 296 种信号分子的浓度。使用高度自动化的无监督算法信息学对结果进行了分析。
结果
质谱细胞仪客观地识别出一种 B 细胞群体，其特征是表达 CD49d、CD69、CD27、CXCR3 和人类白细胞抗原（HLA）-DR，与 MS 明显相关。B 细胞相关因子，特别是 FCRL2 的浓度在 MS CSF 中增加，尤其是在疾病的早期阶段。MS 中 B 细胞营养因子 B 细胞激活因子（BAFF）减少。MS 中涉及神经可塑性的蛋白质也减少。
结论
在没有先验假设的情况下进行分析时，MS 的 CSF 无论是可溶性成分还是细胞成分，都具有与 B 细胞相关的标记物，而 MS 特异性细胞类型的最强候选者具有 B 细胞表型。
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