Analysis and identification of the common genes and molecular pathways of Systemic lupus erythematosus and Rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) are diseases that both result from an immune response that does not correctly recognize self-antigens. In fact, the two diseases share a number of clinical manifestations, immunological features, and genetic characterizations. The aim of this study was to identify the common genetic features, immune cell composition, and molecular mechanisms of SLE and RA. Method Microarray data for RA and SLE in the Gene Expression Omnibus (GEO)database (http://www.ncbi.nlm.nih.gov/geo) was downloaded. We obtained differentially expressed genes (DEGs) for RA and SLE using ‘limma’ package of R software, and subsequently obtained common DEGs for the intersection of these two diseases. GO and KEGG enrichment analyses of these common DEGs were performed. The Protein-protein interaction (PPI) network was constructed from Search Tool for Retrieval of Interacting Genes (STRING) 11.0 and then hub genes were screened by Cytoscape. After verification datasets verification, we obtained five top significant genetic factors from the hub genes. Then, the immune cell infiltration characteristics analysis of RA and SLE were performed using the CIBERSORT algorithm. In addition, microRNAs (miRNAs) for RA and SLE were acquired from the Human MicroRNA Disease Database (HMDD) and their target genes were to be predicted by miRNA-target interactions database (miRTarbase). The miRNAs–mRNAs network was constructed with intersecting genes and miRNAs. At last, drug candidates for top significant genetic factors were forecasted by the Drug Signature Database (DSigDB). Results Using the 'limma' package of R, 232 DEGs for RA, 302 DEGs for SLE, and 52 common DEGs (44 up-regulated and 8 down-regulated) were obtained. Pathway of negative regulation of viral genome replication is most enriched in both RA and SLE. IFI44, IFI44L, IFI6, IFIT3 and PLSCR1 were finally validated as the top significant genetic factors. Dendritic cells activated infiltration was significantly associated with the five top significant genetic factors. The miRNA-mRNA network showed hsa-miR-146a may regulate three top significant genetic factors and play a critical role in RA and SLE. Conclusions IFIT3, IFI44, IFI44L, IFI6 and PLSCR1 were identified as relevant genetic markers for the co-occurrence of RA and SLE, which could be considered as promising clues for the treatment of them.