Bulk and Single-Cell Transcriptome Analysis Reveal Shared Key Genes and Patterns of Immune Dysregulation in Sepsis and Systemic Lupus Erythematosus

Abstract

Abstract Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multi-organ dysfunction. SLE patients are at an elevated risk of sepsis due to immune dysregulation. Sepsis is a life-threatening condition resulting from dysregulated responses to infection and is the leading cause of ICU admission and death in SLE patients. However, the common mechanism of immune dysregulation shared between these two diseases still remains unclear. Methods: Sepsis and SLE datasets were harvested from the Gene Expression Omnibus and Single Cell Portal database. Differential expression and weighted gene co-expression network analysis (WGCNA) were used to identify essential hub genes crucial to sepsis and SLE. The least absolute shrinkage and selection operator (LASSO) regression was used to establish a diagnostic model for SLE, and a receiver operating characteristic (ROC) curve was performed to assess the diagnostic efficiency of the model for SLE and individual genes for sepsis. Single-cell RNA sequencing data of PBMCs from patients with sepsis or SLE were analyzed to evaluate the proportion of different immune cell types. The expression profiles of hub genes in sepsis and SLE patients were further investigated, and similar pathway changes were explored by Gene Set Enrichment Analysis and Gene Ontology (GO) enrichment analysis. Results: We identified 49 co-upregulated and 44 co-downregulated genes between sepsis and SLE datasets. GO analyses of these differentially expressed genes (DEGs) showed that they mainly affected the defence response to the bacteria and immune response. Combined DEGs and WGCNA analysis, we identified 11 hub genes: ANKRD22, RSPH9, DHRS9, AIM2, CCNA1, CEACAM1, FBXO6, TNFAIP6, FCGR1A, PLSCR1, and FCGR1BP. LASSO regression analysis and ROC curve highlighted TNFAIP6 and PLSCR1 as key genes with strong diagnostic values for sepsis and SLE. Single-cell RNA analysis showed an elevated proportion of CD14+ monocytes in sepsis and SLE patients, and hub gene expression was significantly increased in this group. Meanwhile, CD14+ monocytes in these two diseases shared some common transcriptional changes. Conclusion: TNFAIP6 and PLSCR1 are essential genes with strong diagnostic values for sepsis and SLE. In addition, the proportion of CD14+ monocytes within PBMCs of sepsis and SLE patients increased, with indications of some shared transcriptional changes.