Peripheral Immune pattern in a genetic cohort of p.A53T alpha-synuclein carriers

IF 3.1 3区医学 Q2 CLINICAL NEUROLOGY

Parkinsonism & related disorders Pub Date : 2025-04-29 DOI:10.1016/j.parkreldis.2025.107853

Christos Koros , Athina-Maria Simitsi , Nikolaos Papagiannakis , Roubina Antonelou , Anastasia Bougea , Dimitra Papadimitriou , Ioanna Pachi , Ion Beratis , Dionysia Kontaxopoulou , Stella Fragkiadaki , Evangelos Sfikas , Ioanna Alefanti , Chrysa Chrysovitsanou , Efthalia Angelopoulou , Marianna Bregianni , Konstantinos Lourentzos , Vasilios C. Constantinides , Georgios Velonakis , Vasilios Prassopoulos , Anastasios Bonakis , Leonidas Stefanis

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引用次数: 0

Abstract

Introduction

Previous research has shown that inflammatory immune biomarkers including peripheral white blood cell subpopulations differ between Parkinson's disease (PD) patients and healthy controls (HC), with PD exhibiting higher neutrophil to lymphocyte ratio (NLR). The aim of the present report was to assess the peripheral immune profile in patients or asymptomatic carriers harboring the p.A53T alpha-synuclein (SNCA) mutation.

Methods

Data regarding 31 p.A53T SNCA PD patients, 9 asymptomatic mutation carriers and 194 HCs were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on peripheral immune blood cells subpopulations and clinical/imaging parameters at baseline.

Results

NLR, Absolute Neutrophil cell count and Neutrophils to total Leukocytes ratio were increased in the p.A53T SNCA PD group as compared to HCs [2.77 vs 2.18 (p < 0.001), 4.32 × 10^3 cells/μL vs 3.67 × 10^3 cells/μL (p = 0.001), 65.67 % vs 59.55 % (p < 0.001)]. Differences in NLR were mainly driven by the male patient subgroup. Lymphocytes to total Leukocytes and Monocytes to total Leukocytes ratio were lower in the p.A53T SNCA cohort as compared to HC [(p = 0.001) and (p = 0.002)]. Finally, we observed a positive correlation between the absolute Lymphocyte count and the mean putamen DATSCAN signal. Asymptomatic carriers did not differ statistically from either group.

Discussion

Our current study provides evidence of a specific pattern of peripheral immune response in the p.A53T SNCA PD group which aligns well with literature data in idiopathic and GBA-PD. Whether this peripheral immune activation represents a contributing cause or an effect of the neurodegenerative process will require further study.

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p.A53T α -突触核蛋白携带者遗传队列的外周免疫模式

先前的研究表明，包括外周血白细胞亚群在内的炎症免疫生物标志物在帕金森病（PD）患者和健康对照组（HC）之间存在差异，PD表现出更高的中性粒细胞与淋巴细胞比率（NLR）。本报告的目的是评估携带p.A53T α -突触核蛋白（SNCA）突变的患者或无症状携带者的外周免疫特征。方法从帕金森进展标志物倡议（PPMI）数据库中获取31例p.A53T SNCA PD患者、9例无症状突变携带者和194例hc的数据。重点放在外周免疫血细胞亚群和基线的临床/成像参数上。结果与hc相比，p. a53t SNCA PD组snlr、绝对中性粒细胞计数和中性粒细胞与总白细胞之比均升高[2.77 vs 2.18 (p <；0.001), 4.32×10 ^ 3细胞/μL和3.67×10 ^ 3细胞/μL (p = 0.001), 65.67% vs 59.55% (p & lt;0.001)]。NLR的差异主要由男性患者亚组驱动。与HC相比，p. a53t SNCA队列中淋巴细胞与总白细胞和单核细胞与总白细胞的比率较低[（p = 0.001）和（p = 0.002）]。最后，我们观察到绝对淋巴细胞计数与壳核平均DATSCAN信号呈正相关。两组无症状携带者无统计学差异。我们目前的研究提供了p.A53T SNCA PD组特定外周免疫反应模式的证据，这与特发性和GBA-PD的文献数据很好地吻合。这种外周免疫激活是否代表神经退行性过程的促成原因或结果将需要进一步研究。

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

Parkinsonism & related disorders 医学-临床神经学

CiteScore

6.20

自引率

4.90%

发文量

292

审稿时长

39 days

期刊介绍： Parkinsonism & Related Disorders publishes the results of basic and clinical research contributing to the understanding, diagnosis and treatment of all neurodegenerative syndromes in which Parkinsonism, Essential Tremor or related movement disorders may be a feature. Regular features will include: Review Articles, Point of View articles, Full-length Articles, Short Communications, Case Reports and Letter to the Editor.