Characterization of virus-mediated autoimmunity and the consequences for pathological process in patients with systemic lupus erythematosus.

Abstract

This study aimed to identify differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus (GEO) database. The significantly enriched immune and virus-related gene lists were computed and visualized by using the DEGs from the gene set enrichment analysis (GSEA). Quantification of 38 immune cells was performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQuant algorithm. Thirty-nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways in 26 female SLE patients. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein-Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. Identifying virus-mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of female SLE, and will lead to clinical tools for treating SLE in patients. Key Points • Using gene expression-based computational methodologies,the 57immune and viral genes were significantly upregulated in 26 SLE patients. • The identifiedthree key viral genessuch as OAS1, OAS2, and IF7 were closely associated with colony-forming unit-monocytes and colony-forming unit-granulocytes, which affect the virus mediated immunity in SLE. • The viral genes and quantifies of immune cells are useful in understanding pathogenesis of SLE, and this will provide clinical strategiesof potential treatment choicesin SLE patients.