Abstract
BACKGROUND: The interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) gene is strongly associated with disease activity index of childhood systemic lupus erythematosus (SLE). However, whether IFIT1-regulated gene expression is the molecular basis of the pathogenesis of SLE has not been fully investigated. METHODS: Dataset GSE11909 was used to analyze the expression profiles of IFIT1 gene in 103 SLE cases and 12 healthy individuals. Differentially expressed genes (DEGs)-affected by IFIT1 gene were screened between the case group and control group, followed by gene function analysis. The clinical diagnostic potential of the least absolute shrinkage and selection operator (LASSO) model, established based on the expression profiles of IFIT1 and IFIFT1-affected DEGs, was evaluated. Analysis of association between IFIFT1-affected DEGs and immune infiltration was performed. RESULTS: IFIT1 was highly expressed in childhood SLE patients. IFIT1 and IFIT1-affected DEGs showed the potential to serve as a diagnostic marker for childhood SLE with area under the curve (AUC) value of 0.947. Childhood SLE patients showed 826 upregulated DEGs and 4,111 downregulated DEGs compared to the control group. Among them, 208 upregulated DEGs and 214 downregulated DEGs were identified in the IFIT1-high group compared to the IFIT1-low group. The LASSO model for the diagnosis of childhood SLE involved 7 marker genes that were related to immune checkpoint and tertiary lymphoid structure in SLE. CONCLUSIONS: Our results confirmed the clinical diagnostic potential of IFIT1 and IFIT1-affected genes in childhood SLE. Moreover, this study elucidated that IFIT1-induced changes in the transcriptome are involved in immune checkpoint and tertiary lymphoid structure in childhood.