Deecke Laura, Goldeck David, Ohlei Olena, Homann Jan, Demuth Ilja, Bertram Lars, Pawelec Graham, Lill Christina M
Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Department of Immunology, University of Tübingen, 72076 Tübingen, Germany.
Int J Mol Sci. 2024 Dec 20;25(24):13655. doi: 10.3390/ijms252413655.
The immune system likely plays a key role in Parkinson's disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs ( = 87) from a large genome-wide association study ( = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells ( = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells ( = 0.019) and CD27+CD4+ memory T cells ( = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.
免疫系统可能在帕金森病(PD)的病理生理学中起关键作用。因此,我们研究了在具有高PD遗传风险的健康个体中免疫细胞组成是否已经发生改变。我们使用多色流式细胞术对442名个体血液中的92种免疫细胞亚型进行了定量分析。基于一项大型全基因组关联研究(n = 1,530,403)中全基因组显著的单核苷酸多态性(SNP,n = 87)计算了PD的多基因风险评分(PGS)。线性回归分析未发现PGS与任何免疫细胞亚型之间存在显著关联(FDR = 0.05)。在总体样本中,观察到NKG2C+B细胞存在名义上显著的关联(P = 0.026)。遗传PD风险增加的老年参与者还表现出较高比例的髓样树突状细胞(P = 0.019)和CD27+CD4+记忆T细胞(P = 0.043)。仅在女性中,几种免疫细胞存在名义上的统计学关联。这些发现表明,免疫细胞的主要改变仅在PD进展后期才会出现。