Objectives: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide. It is difficult to explain the heterogeneity of the clinical presentation and prognosis as the pathogenesis is not completely understood yet. We performed transcriptome profiling of peripheral immune cells of IgAN to explore the role of immune cells in the pathogenesis of IgAN. Methods: Peripheral blood mononuclear cells were obtained from 20 IgAN patients and 9 healthy controls. The cells were FACS sorted into B, CD4 T, and CD8 T subsets. Single cell RNA sequencing (scRNA-seq) was performed using NovaSeq6000. The patients were divided into mild to moderate and severe group, according to the eGFR and proteinuria value. The differentially expressed genes (DEG) were identified. Pathway analysis was performed with Ingenuity Pathway Analysis. Results: After quality control, 32,742 B cells, 101,637 CD4 T cells, 63,029 CD8 T cells were retained for further analysis. Annatated cell clusters were presented in UMAP. (Figure 1) Ninety five genes were commonly upregulated in all subsets of IgAN, including AKT1, CD81, JUN and TGFB1. (Figure 2) Compared to the mild to moderate IgAN group, severe IgAN group exhibited the significant increase in DEG expression; 40, 148, 132 upregulated and 233, 77, 78 downregulated DEGs in B, CD4 T, CD8 T cell subsets, respectively. Upregulated DEGs in B and CD4 T cell subsets were associated with eukaryotic translation pathways. The upstream analysis predicted the top transcriptional regulators; ETV3 was significantly activated upstream regulator in all subsets of severe IgAN and regulated the downstream target genes including IFIT3, SAMD9L and XAF1. Conclusions: The present transcriptome profiling showed different gene expression profiles according to the severity of IgAN. The study provides new insights into the role of immune cells in understanding the pathogenesis of IgAN. The present study may contribute to the investment of the novel disease specific biomarkers of IgAN.