Transcriptome-based gene enrichment and immune cell infiltration analysis in patients with bipolar disorder

Wang Xiaobo; Wang Yumei; Zhang Tianle; Xie Tingting; Su Yu

doi:10.3969/j.issn.1009-6574.2025.07.002

Abstract：Objective To explore the overall expression of mRNA in peripheral blood mononuclear cell(PBMC)of patients with bipolar disorder(BD)and analyze the immune infiltration.Methods From October 2022 to July 2023,24 patients with BD and 12 healthy controls(HC)attending the Mental Health Center of the First Hospital of Hebei Medical University were selected for the study.Genome-wide gene expression profiles in PBMC of 36 enrollees were analyzed using microarrays for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Protein-protein interaction(PPI)analysis was performed and immune cell infiltration and its interrelationships were assessed using gene set variation analysis(GSVA).Results A total of 304 differentially expressed genes(DEGs)were identified in BD versus HC comparisons,of which 217 genes were upregulated and 87 genes were downregulated.Enrichment analysis suggested that biological processes and signaling pathways related to extracellular matrix,stress response,heparin binding,and immune inflammation were upregulated in BD group.In the IL-17 pathway,Jun,Fosb,Fosl1,TNFAIP3,NFKBIA,CXCL2,CXCL8,IL6,and IL17C gene expression was upregulated in BD patients compared to HC.Real-time quantitative reverse transcription PCR(qRT-PCR)analysis showed that Jun,Fosb,Fosl1,NFKBIA,TNFAIP3,CXCL2 and CXCL8 gene expression were upregulated in BD,but only Jun,Fosl1,NFKBIA,CXCL2 and CXCL8 changes were statistically significant(all P＜0.05).Immune infiltration analysis showed that central memory CD4+T cells(P=0.010),eosinophils(P=0.038)and mast cells(P=0.029)were infiltrated increased in BD group,and there were positive correlations between effector memory CD8+T cells and activated CD8+T cells and T follicular helper cells,and the differences were statistically significant(r=0.56,0.58,both P＜0.05).Conclusions This study integrates transcriptomics and immune microenvironment analysis to reveal characteristic changes in the peripheral immune system of BD patients,suggesting that the peripheral immune system may be involved in the pathogenesis of BD through chemokine-induced inflammatory responses.Immune infiltration analysis reveals the presence of a chronic immune activation state in patients with BD.