Systemic lupus erythematosus (SLE), a multisystem autoimmune disease, often shares overlapping features (immune dysregulation, dry mouth/dry eyes, joint pain) with Sjögren’s syndrome (SS)—which can be primary (pSS) or secondary to SLE. This study focuses on their shared gene signatures, using bioinformatics to mine common molecular characteristics. It aims to reveal core pathways (e.g., innate/adaptive immune dysregulation, cytokine storm) driving both diseases, providing key evidence for understanding cross-pathogenesis, developing combined diagnostic biomarkers, and precision targeted therapies.

SLE-related gene expression datasets (GSE50772 and GSE81622) and pSS-related datasets (GSE84844 and GSE48378), which were derived from peripheral blood mononuclear cells (PBMCs) samples, were integrated. Based on differential expression analysis, significantly up - regulated or down - regulated differentially expressed genes (DEGs) were screened. A protein - protein interaction (PPI) network was constructed, and Gene Ontology (GO) functional annotation and KEGG pathway enrichment analysis were conducted on the DEGs to systematically analyze their potential biological functions and signaling pathway mechanisms.

A total of 232 and 110 differentially expressed genes (DEGs) were identified in the SLE and primary pSS datasets, respectively. A total of 32 common DEGs were identified, all of which were up - regulated in patients when compared to controls. Among these 32 DEGs, 11 genes (IFI27, IFI44L, RSAD2, IFIT1, IFI44, USP18, IFI6, HERC5, EPSTI1, OAS1, OAS3) exhibited an expression fold - change greater than 2 across all datasets. Protein - protein interaction (PPI) analysis indicated that there were interactions among 29 genes. Gene Ontology (GO) analysis demonstrated that the 32 shared DEGs were primarily enriched in the type Ⅰ interferon signaling pathway, defense response to virus, response to virus, negative regulation of viral genome replication, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these 32 DEGs were associated with viral infection.

This study showed that the change of biological process associated with response to virus infection play critical roles during both SLE and pSS.