Abstract

Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8+ T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8+ T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.

Highlights

  • Parkinson’s disease (PD) is the second most common neurodegenerative disorder; it is characterized by progressive dopaminergic neuron death and Lewy body, α-synuclein, accumulation[1]

  • Mass cytometry profiling was performed in 40 peripheral blood mononuclear cell (PBMC) samples of 40 subjects; among them, 10 had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 were age- and sex-matched young healthy controls (YHCs) and 8 were elder HCs (EHCs)

  • Normalized abundances were compared between patients with PD and HCs and among the four subgroups (EOPD, LOPD, YHCs, and EHCs)

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Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder; it is characterized by progressive dopaminergic neuron death and Lewy body, α-synuclein, accumulation[1]. Previous studies have shown that the peripheral immune cells and molecules contribute to the development of PD through infiltration of the central nervous system (CNS) from an impaired blood–brain barrier. Α-synuclein reactive T cells could even be detected even 10 years prior to PD diagnosis; this supports the role of immune inflammation in the pathogenesis of PD8. Dysregulation of both the innate and adaptive immune systems in the peripheral blood of patients with PD has recently been documented[9,10]. In the peripheral blood of PD patients, CD8+ T cells[6], monocytes[14], and NK cells[10] are commonly increased; CD4+ T cells[15] are decreased

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