Integrated Bioinformatics Analysis of the IRF5 Signalling Pathway in Children with Systemic Lupus Erythematosus

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and is characterised by various symptoms such as fatigue, fever, joint pain and swelling, skin rashes, and inflammation of the kidneys or brain. Children with SLE may experience additional symptoms, such as delayed puberty. The main objective of the study is to perform an integrated bioinformatics analysis of the interferon regulatory factor 5 (IRF5) signalling pathway in children with SLE. Methods: We obtained two microarray datasets from the Gene Expression Omnibus (GEO) database. The Gene Set Enrichment (GSE17926) dataset, based on the GPL9059 platform, consists of 13 and 37 IRF5 samples. The GSE81622 dataset was based on the GPL10558 platform and consisted of 30 SLE patients and 25 controls. Data normalisation and relevant plots were produced in R software. We visualized the protein-protein interaction (PPI) networks using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and performed gene ontology and pathway enrichment analysis using ShinyGO. Results: We identified 357 differentially expressed genes (DEGs), of which 190 were downregulated while 167 were upregulated. Using the STRING tool, we constructed a PPI network and identified 10 hub genes (interleukin 1 receptor associated kinase 1 (IRAK1), Cyclic adenosine monophosphate-response element binding protein (CREBBP), signal transducer and activator of transcription 1 (STAT1), myeloid differentiation factor 88 (MyD88), interferon simulated gene 15 (ISG15), signal transducer and activator of transcription 2 (STAT2), interferon beta 1 (IFNB1), tumour necrosis receptor-associated factor 6 (TRAF6), rel-associated protein (RELA), and interferon regulatory factor 3 (IRF3) associated with IRF5 signalling in SLE. We also identified three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in IRF5 and the hub genes: the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway, the Toll-like receptor signalling pathway, and the cellular differentiation of T helper cells. Furthermore, we found that IRF5 signalling was enriched in pathways such as response to peptidoglycans, muramyl dipeptide and regulation of interferons. Conclusions: The dysregulation of the IRF5 signalling pathway can contribute to the development of SLE by promoting inflammation and activating the immune system. This can lead to tissue damage and the production of autoantibodies.