核糖核蛋白自身抗体阳性系统性红斑狼疮患者的基因表达谱和免疫途径失调。

Gene Expression Profiling and Immune Pathway Dysregulation in Ribonucleoprotein Autoantibody-Positive Systemic Lupus Erythematosus Patients.

机构信息

School of Life Sciences, Shandong University, Jinan 250012, China.

Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA.

出版信息

Genes (Basel). 2024 Oct 22;15(11):1353. doi: 10.3390/genes15111353.

DOI:10.3390/genes15111353

PMID:39596553

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11593874/

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation and chronic inflammation across various organ systems. While anti-dsDNA and anti-Sm antibodies are commonly associated with SLE, the presence of anti-RNP antibodies is often linked to unique gene expression profiles and immune responses. This study aims to investigate the gene expression profiles in ribonucleoprotein (RNP) autoantibody-positive SLE patients by analyzing publicly available transcriptomic data.

METHODS

This study analyzed transcriptomic data from the GEO dataset GSE61635, which includes gene expression profiles from 79 anti-RNP-positive SLE patients and 30 healthy controls. Differentially expressed genes (DEGs) were identified using the GEO2R tool with a -value < 0.05 and |log2fold change| > 1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Tissue-specific and cell-type enrichment analyses highlighted the involvement of immune tissues.

RESULTS

A total of 1891 DEGs were identified between anti-RNP-positive SLE patients and healthy controls. Among the identified DEGs, and were notably downregulated, while was highly upregulated. Enrichment analyses revealed significant dysregulation in antiviral response and immune regulation pathways. PPI network analysis highlighted key hub genes, suggesting a heightened antiviral state in these patients. Tissue-specific enrichment and cell-type enrichment identified the bone marrow and immune tissues as being highly affected by the altered gene expression. Additionally, gene frequency analysis highlighted as being recurrently significant across multiple studies.

CONCLUSIONS

The findings suggest that anti-RNP-positive SLE patients exhibit distinct gene expression and immune dysregulation profiles, particularly in antiviral and immune regulation pathways. These results provide insights into the molecular mechanisms driving SLE in this patient subset and may guide future therapeutic interventions.

摘要

背景

系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是免疫失调和慢性炎症涉及多个器官系统。虽然抗 dsDNA 和抗 Sm 抗体通常与 SLE 相关，但抗 RNP 抗体的存在通常与独特的基因表达谱和免疫反应相关。本研究旨在通过分析公共转录组数据来研究 RNP 自身抗体阳性 SLE 患者的基因表达谱。

方法

本研究分析了 GEO 数据集 GSE61635 的转录组数据，该数据集包含 79 名抗 RNP 阳性 SLE 患者和 30 名健康对照的基因表达谱。使用 GEO2R 工具，以 - 值 < 0.05 和 |log2fold change| > 1 识别差异表达基因（DEGs）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。组织特异性和细胞类型富集分析突出了免疫组织的参与。

结果

在抗 RNP 阳性 SLE 患者和健康对照之间共鉴定出 1891 个 DEGs。在鉴定出的 DEGs 中，和明显下调，而显著上调。富集分析显示抗病毒反应和免疫调节途径的显著失调。PPI 网络分析突出了关键的枢纽基因，表明这些患者存在高度的抗病毒状态。组织特异性和细胞类型富集分析确定骨髓和免疫组织受到改变的基因表达的强烈影响。此外，基因频率分析突出了在多个研究中反复具有重要意义。