From the The Center for Neuroinflammation and Neurotherapeutics and the Department of Neurology (R.L., L.Z., K.S., A.R., A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Neurology (T.F.T., L.R.B., M.E.D.-O., A.C-P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Bioengineering (M.E.D.-O.), School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia; Department of Cardiology (B.Z.), the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Department of Neurology (R.N.A.), Columbia University, New York, NY.
Neurol Neuroimmunol Neuroinflamm. 2021 Dec 26;9(2). doi: 10.1212/NXI.0000000000001125. Print 2022 Mar.
There has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.
Peripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.
The discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.
Our findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.
免疫系统在帕金森病（PD）发病机制中的潜在作用引起了越来越多的关注。本研究的目的是全面描述 PD 患者与对照组患者循环免疫细胞的表型和功能特征。
在 2 个独立队列（发现和验证）中，从 PD 患者和年龄、性别匹配的神经正常对照组（NC）中采集外周血。对全血白细胞和外周血单核细胞进行综合多色流式细胞术，以鉴定不同的免疫亚群及其体外反应。
发现队列包括 17 名 NC 和 12 名 PD 患者，验证队列包括 18 名 NC 和 18 名 PD 患者。在主要免疫细胞类型中，B 细胞似乎在 PD 中优先受到影响。与对照组相比，PD 患者的增殖 B 细胞计数减少。具有调节能力的 B 细胞亚群（如过渡 B 细胞）的比例在 PD 患者中优先降低，而促炎细胞因子产生 B 细胞的比例增加，导致其 B 细胞功能细胞因子反应呈促炎偏移。无监督主成分分析显示 PD 患者的 B 细胞和 T 细胞表达增加 TNFα 和 GM-CSF。此外，PD 患者滤泡性 T 细胞（一种重要的 B 细胞辅助 T 细胞群体）水平降低，与 B 细胞异常相关。
我们的发现定义了外周免疫细胞的新特征，并提示 PD 患者存在异常的 Tfh:B 细胞相互作用。
