This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between primary Sjögren’s syndrome (pSS) and preeclampsia (PE).

We obtained data on PE and pSS from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected using support vector machine-recursive feature elimination (SVM-RFE) and random forest，and a receiver operating characteristic

(ROC) curve was generated based on the results of this selection. Finally, single-sample

Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cell types in the expression profile and their association with the identified hub genes.

By intersecting the important module genes with the differential expressed genes (DEGs), 116 DEGs identified as key crosstalk genes. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. SVM-RFE and random forest analysis identified insulin-like growth factor 1 receptor (IGF1R), insulin receptor substrate(IRS) 2, and slingshot homolog (SSH)1 as the optimal shared diagnostic biomarkers for both pSS and PE. Additionally, the analysis of immune cell infiltration and key cell types revealed the significant involvement of natural killer (NK) and CD8+ T cell in the pathogenesis of PE and pSS.This study identified IGF1R, IRS2, and SSH1 as biomarkers in PE associated with SS. Integrated analysis results from GO, GeneMANIA, GSEA, and functional enrichment of key cells collectively suggest that the abnormal regulation of the insulin signaling pathway may be a significant common feature in the pathogenesis of both PE and SS. Furthermore, based on comprehensive single-cell analysis and references, B cells, CD8⁺ T cells, and NK cells were identified as key cell types. However, this study has certain limitations, such as a limited sample size and methodological constraints, which may lead to some discrepancies between our findings and existing reports. Nevertheless, we will continue to focus on the roles of these mechanisms in PE and SS. 

This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between PE and pSS. This study preliminarily revealed activated CD4+ T cell, NK cell, and CD8+T cell and downregulation of IGF1R pathway in the pathogenesis of both conditions.