Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis

Abstract

Objective: The present investigation is aimed at identifying key immune-related genes linked with SLE and their roles using integrative analysis of publically available gene expression datasets.

Methods: Four gene expression datasets pertaining to SLE, 2 from whole blood and 2 experimental PMBC, were sourced from GEO. Shared differentially expressed genes (DEG) were determined as SLE-related genes. Immune cell infiltration analysis was performed using CIBERSORT, and case samples were subjected to k-means cluster analysis using high-abundance immune cells. Key immune-related SLE genes were identified using correlation analysis with high-abundance immune cells and subjected to functional enrichment analysis for enriched Gene Ontology Biological Processes and KEGG pathways. A PPI network of genes interacting with the key immune-related SLE genes was constructed. LASSO regression analysis was performed to identify the most significant key immune-related SLE genes, and correlation with clinicopathological features was examined.

Results: 309 SLE-related genes were identified and found functionally enriched in several pathways related to regulation of viral defenses and T cell functions. k-means cluster analysis identified 2 sample clusters which significantly differed in monocytes, dendritic cell resting, and neutrophil abundance. 65 immune-related SLE genes were identified, functionally enriched in immune response-related signaling, antigen receptor-mediated signaling, and T cell receptor signaling, along with Th17, Th1, and Th2 cell differentiation, IL-17, NF-kappa B, and VEGF signaling pathways. LASSO regression identified 9 key immune-related genes: DUSP7, DYSF, KCNA3, P2RY10, S100A12, SLC38A1, TLR2, TSR2, and TXN. Imputed neutrophil percentage was consistent with their expression pattern, whereas anti-Ro showed the inverse pattern as gene expression.

Conclusions: Comprehensive bioinformatics analyses revealed 9 key immune-related genes and their associated functions highly pertinent to SLE pathogenesis, subtypes, and identified valuable candidates for experimental research.