Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren’s syndrome based on integrated bioinformatics and single-cell RNA-seq analysis

作者：Yanling Cui, Huina Zhang, Zhen Wang, Bangdong Gong, Hisham Al-Ward, Yaxuan Deng, Orion Fan, Junbang Wang, Wenmin Zhu, Yi Sun · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1212330 · 被引用次数：36 · 研究领域：Salivary Gland Disorders and Functions、Single-cell and spatial transcriptomics、Systemic Lupus Erythematosus Research

Background Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS. Methods Gene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets. Results Following WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely IFI44L, ISG15, IFIT1, USP18, RSAD2 and ITGB2 , out of which three genes, namely IFI44L, ISG15 and ITGB2 were found to be highly expressed in both microarray and scRNA-seq datasets. IFN r...