Peripheral mononuclear cells and systemic lupus erythematosus association: Integrated study of single-cell sequencing and mendelian randomization analysis.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY Lupus Pub Date : 2024-10-15 DOI:10.1177/09612033241292705
Shi Jian, Han Li
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Abstract

Objective: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease predominantly affecting women. Despite advances in treatment, recent developments in single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR) continue to facilitate the need for precision medicine.

Methods: Data obtained from the GSE135779 dataset underwent quality control, normalization, and dimensionality reduction using Seurat and MonacoImmuneData. Marker genes identified subgroups for analysis with CellChat and ClusterProfilerR. MR analysis of these genes' eQTLs was performed to establish causal relationships with SLE using IEU Open GWAS project data.

Results: Single-cell analysis revealed distinct cellular subtypes and highlighted increased monocyte levels in patients with SLE. MR analysis revealed 12 genes, particularly interferon induced protein with tetratricopeptide repeats 3 (IFIT3), causally related to SLE. Gene ontology and the Kyoto encyclopedia of genes and genomes analyses identified pathways significant to SLE pathogenesis. Visualization of these genes at the single-cell level revealed their role in disease progression. Cell communication differences between IFIT3-positive and -negative groups were also observed.

Conclusion: This study demonstrates the potential of scRNA-seq and MR in identifying critical factors in SLE pathogenesis, thereby supporting the need for targeted therapies. Identifying IFIT3, among other genes, as central to SLE progression opens new avenues for precision medicine approaches in SLE management.

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外周单核细胞与系统性红斑狼疮的关联:单细胞测序和孟德尔随机分析的综合研究。
目的:系统性红斑狼疮(SLE)是一种主要影响女性的复杂自身免疫性疾病。尽管在治疗方面取得了进展,但单细胞RNA测序(scRNA-seq)和孟德尔随机化(MR)的最新发展继续促进了对精准医疗的需求:从 GSE135779 数据集获得的数据使用 Seurat 和 MonacoImmuneData 进行了质量控制、归一化和降维处理。标记基因通过 CellChat 和 ClusterProfilerR 确定了用于分析的亚组。利用 IEU Open GWAS 项目数据对这些基因的 eQTLs 进行磁共振分析,以确定与系统性红斑狼疮的因果关系:结果:单细胞分析揭示了系统性红斑狼疮患者不同的细胞亚型,并强调了单核细胞水平的升高。磁共振分析发现了 12 个与系统性红斑狼疮有因果关系的基因,尤其是具有四肽重复序列 3 的干扰素诱导蛋白(IFIT3)。基因本体论和京都基因与基因组百科全书分析确定了与系统性红斑狼疮发病机制相关的重要通路。这些基因在单细胞水平上的可视化显示了它们在疾病进展中的作用。还观察到了IFIT3阳性组和阴性组之间的细胞通讯差异:这项研究表明,scRNA-seq 和磁共振技术在确定系统性红斑狼疮发病机制的关键因素方面具有潜力,从而支持了靶向疗法的需求。确定 IFIT3 和其他基因是系统性红斑狼疮进展的关键因素,为系统性红斑狼疮的精准治疗开辟了新的途径。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
期刊最新文献
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