SERPINA3 and NDRG1 are critical diagnostic immune genes associated with macrophages in preeclampsia.

Preeclampsia (PE) is a pregnancy complication involving immune dysregulation. This study aims to identify diagnostic immune biomarkers for PE using machine learning. mRNA expression profiles from GSE75010 and immune-related genes from ImmPort were analyzed. Differentially expressed immune-related genes (DIRGs) were identified and subjected to GO/KEGG enrichment, PPI network, LASSO, and mSVM-RFE analyses. Candidate biomarkers were validated in additional GEO datasets (GSE54618, GSE74341, GSE147776) and by RT-PCR, Western blot, and immunohistochemistry in placental tissues. Immune cell infiltration was evaluated using CIBERSORT. Ten DIRGs were identified between PE and normotensive pregnancies. GO/KEGG analyses highlighted cytokine-cytokine receptor interactions. SERPINA3 and NDRG1 were identified as diagnostic biomarkers (AUC = 0.812 and 0.866 in training set; 0.798 and 0.781 in test set). Elevated expression of SERPINA3 and NDRG1 was confirmed in PE placental tissues. Immune analysis revealed that both genes were negatively correlated with M2 macrophages. SERPINA3 and NDRG1 are critical immune-related diagnostic biomarkers for PE and are associated with M2 macrophage reduction, providing novel insights into PE pathogenesis and diagnosis.