关键词: Alzheimer's disease Blood biomarkers CD8+ T cell scRNA-seq

Mesh : Humans Granzymes Resistin Transcriptome Alzheimer Disease / genetics CD8-Positive T-Lymphocytes Biomarkers

来  源:   DOI:10.12182/20230960107   PDF(Pubmed)

Abstract:
UNASSIGNED: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer\'s disease (AD) as biomarkers.
UNASSIGNED: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package.
UNASSIGNED: There were two kinds of CD8 + T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K ( GZMK) (false discovery rate [FDR]<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK + CD8 + T cells was increased by 32.9% ( P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA- A, HLA- B, HLA- C, and HLA- E, for the abnormal MHC-Ⅰ signaling pathway of GZMK + CD8 + T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients.
UNASSIGNED: The increased content of peripheral blood GZMK + CD8 + T cells, the increased interaction between GZMK + CD8 + T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.
摘要:
基于单细胞RNA测序(scRNA-seq)探索阿尔茨海默病(AD)患者外周血中作为生物标志物的免疫特征。
GSE168522,AD外周血免疫细胞的scRNA-seq数据集,从基因表达综合(GEO)数据库下载,并在RAD-Blood网络服务器(http://www.生物信息。cn/RAD-Blood/)。分析AD患者血细胞组成的变化。采用CellChatR软件包对AD患者不同类型细胞间的异常通讯进行了研究。
AD患者和健康个体的血液中有两种CD8+T细胞,其中高表达颗粒酶K(GZMK)(假发现率[FDR]<0.05),和另一种高表达的GZMA,GZMB,和GZMH(FDR<0.05)。在AD患者的血液中,GZMK+CD8+T细胞含量增加32.9%(P=5.15E-21),它们与其他细胞类型的相互作用增加,它们可能通过主要组织相容性复合体Ⅰ类(MHC-Ⅰ)的异常信号转导与AD相关。红细胞提供了主要的配体,那就是,人类白细胞抗原(HLA)Ⅰ类分子,包括HLA-A,HLA-B,HLA-C,和HLA-E,GZMK+CD8+T细胞MHC-Ⅰ信号通路异常。RESISTIN信号通路在AD患者血液中特异性富集。
外周血GZMK+CD8+T细胞含量增加,GZMK+CD8+T细胞和红细胞之间的相互作用增加,增强的抵抗素途径是AD的潜在血液生物标志物。
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