背景:免疫系统异常激活是帕金森病的重要发病机制,但是外周炎症之间的关系,中央小胶质细胞激活和多巴胺能变性仍不清楚。
目的:评估脑内小胶质细胞活化及其与临床严重程度的关系,多巴胺能突触前功能,以及与适应性免疫相关的外周炎症生物标志物。
方法:在本病例对照研究中,我们招募了23名健康参与者和24名早期帕金森病参与者.18F-PBR06PET/MR用于小胶质细胞激活,18F-FP-DTBZ用于多巴胺能神经支配,T细胞和T辅助细胞亚群(Th1/Th2/Th17)的总账户,并评估血清炎性细胞因子水平。Sanger测序用于排除18F-PBR06-PET的混合亲和结合剂。
结果:与健康对照组相比,帕金森病患者的18F-PBR06-PET标准摄取值比值(SUVR)增加,特别是在运动发作的同侧。18F-PBR06-PETSUVR与脑干18F-FP-DTBZ-PETSUVR呈正相关,与Hoehn和Yahr分期测量的疾病严重程度无关。MDS-UPDRSIII评分。与健康对照组相比,帕金森病患者的Th1细胞频率和血清IL10和IL17A水平升高。未观察到外周炎症标志物与PD脑中小胶质细胞活化之间的显著关联。
结论:帕金森病与早期卵黄小胶质细胞活化和外周表型Th1偏倚有关。外周适应性免疫可能间接参与PD神经变性过程中小胶质细胞的激活,可能是早期检测的潜在生物标志物和免疫调节治疗的靶标。
BACKGROUND: Abnormal activation of immune system is an important pathogenesis of Parkinson\'s disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear.
OBJECTIVE: To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity.
METHODS: In this case-control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson\'s disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET.
RESULTS: Compared to healthy controls, patients with Parkinson\'s disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson\'s disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed.
CONCLUSIONS: Parkinson\'s disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.