Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Department of Dermatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Front Immunol. 2024 May 7;15:1354348. doi: 10.3389/fimmu.2024.1354348. eCollection 2024.
Systemic lupus erythematosus (SLE) is a multi-organ chronic autoimmune disease. Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract. Previous studies have shown that SLE and IBD share common pathogenic pathways and genetic susceptibility, but the specific pathogenic mechanisms remain unclear.
The datasets of SLE and IBD were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the Limma package. Weighted gene coexpression network analysis (WGCNA) was used to determine co-expression modules related to SLE and IBD. Pathway enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for co-driver genes. Using the Least AbsoluteShrinkage and Selection Operator (Lasso) regressionand Support Vector Machine-Recursive Feature Elimination (SVM-RFE), common diagnostic markers for both diseases were further evaluated. Then, we utilizedthe CIBERSORT method to assess the abundance of immune cell infiltration. Finally,we used the single-cell analysis to obtain the location of common diagnostic markers.
71 common driver genes were identified in the SLE and IBD cohorts based on the DEGs and module genes. KEGG and GO enrichment results showed that these genes were closely associated with positive regulation of programmed cell death and inflammatory responses. By using LASSO regression and SVM, five hub genes (KLRF1, GZMK, KLRB1, CD40LG, and IL-7R) were ultimately determined as common diagnostic markers for SLE and IBD. ROC curve analysis also showed good diagnostic performance. The outcomes of immune cell infiltration demonstrated that SLE and IBD shared almost identical immune infiltration patterns. Furthermore, the majority of the hub genes were commonly expressed in NK cells by single-cell analysis.
This study demonstrates that SLE and IBD share common diagnostic markers and pathogenic pathways. In addition, SLE and IBD show similar immune cellinfiltration microenvironments which provides newperspectives for future treatment.
系统性红斑狼疮（SLE）是一种多器官慢性自身免疫性疾病。炎症性肠病（IBD）是一种常见的胃肠道慢性炎症性疾病。先前的研究表明，SLE 和 IBD 具有共同的发病途径和遗传易感性，但具体的发病机制仍不清楚。
从基因表达综合数据库（GEO）下载 SLE 和 IBD 的数据集。使用 Limma 包识别差异表达基因（DEGs）。使用加权基因共表达网络分析（WGCNA）确定与 SLE 和 IBD 相关的共表达模块。对共驱动基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析的通路富集。使用最小绝对收缩和选择算子（Lasso）回归和支持向量机-递归特征消除（SVM-RFE）进一步评估两种疾病的共同诊断标志物。然后，我们利用 CIBERSORT 方法评估免疫细胞浸润的丰度。最后，我们使用单细胞分析获得共同诊断标志物的位置。
根据 DEGs 和模块基因，在 SLE 和 IBD 队列中确定了 71 个共同的驱动基因。KEGG 和 GO 富集结果表明，这些基因与程序性细胞死亡和炎症反应的正调控密切相关。通过使用 LASSO 回归和 SVM，最终确定了五个枢纽基因（KLRF1、GZMK、KLRB1、CD40LG 和 IL-7R）作为 SLE 和 IBD 的共同诊断标志物。ROC 曲线分析也显示出良好的诊断性能。免疫细胞浸润的结果表明，SLE 和 IBD 具有几乎相同的免疫浸润模式。此外，通过单细胞分析，大多数枢纽基因在 NK 细胞中共同表达。
本研究表明，SLE 和 IBD 具有共同的诊断标志物和发病途径。此外，SLE 和 IBD 表现出相似的免疫细胞浸润微环境，为未来的治疗提供了新的视角。
