Carlisle Samantha M, Qin Hongwei, Hendrickson R Curtis, Muwanguzi Jordana E, Lefkowitz Elliot J, Kennedy Richard E, Yan Zhaoqi, Yacoubian Talene A, Benveniste Etty N, West Andrew B, Harms Ashley S, Standaert David G
Alabama Morris K. Udall Center of Excellence in Parkinson's Disease Research, University of Alabama at Birmingham, 1719 Sixth Ave. South, Birmingham, AL, USA.
Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL, USA.
NPJ Parkinsons Dis. 2021 Apr 13;7(1):36. doi: 10.1038/s41531-021-00180-z.
Increasing evidence supports the role of brain and systemic inflammation in the etiology of Parkinson disease (PD). We used gene expression profiling to examine the activation state of peripheral blood monocytes in 18 patients with early, untreated PD and 16 healthy control (HC) subjects. Monocytes were isolated by negative selection, and gene expression studied by RNA-seq and gene set enrichment analysis. A computational model that incorporated case/control status, sex, and the interaction between case/control status and sex was utilized. We found that there was a striking effect of sex on monocyte gene expression. There was inflammatory activation of monocytes in females with PD, with enrichment of gene sets associated with interferon gamma stimulation. In males, the activation patterns were more heterogeneous. These data point to the importance of systemic monocyte activation in PD, and the importance of studies which examine the differential effects of sex on pathophysiology of the disease.
越来越多的证据支持大脑和全身炎症在帕金森病（PD）病因学中的作用。我们使用基因表达谱分析来检查18例未经治疗的早期PD患者和16名健康对照（HC）受试者外周血单核细胞的激活状态。通过阴性选择分离单核细胞，并通过RNA测序和基因集富集分析研究基因表达。使用了一个纳入病例/对照状态、性别以及病例/对照状态与性别之间相互作用的计算模型。我们发现性别对单核细胞基因表达有显著影响。患有PD的女性单核细胞存在炎症激活，与干扰素γ刺激相关的基因集富集。在男性中，激活模式更为异质。这些数据表明全身单核细胞激活在PD中的重要性，以及研究性别对该疾病病理生理学差异影响的重要性。
