Identification of Lupus-Associated Genes in the Pathogenesis of Pre-eclampsia Via Bioinformatic Analysis.

Abstract

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE.