Kidney Week

Abstract: TH-PO541

Investigation of Molecular Insights into the Disease-Specific Pathophysiology of IgA Nephropathy Using Single-Cell RNA Sequencing

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Lee, Soojin, Eulji University Uijeongbu Eulji Medical Center, Uijeongbu, Gyeonggi-do, Korea (the Republic of)

Soojin Lee, MD, PhD

• Kim, Gwanghun, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Gwanghun Kim, PhD

• Koh, Jung Hun, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Jung Hun Koh, MD

• Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Sehoon Park, MD, PhD

• Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)

Yaerim Kim, MD, PhD

• Kim, Hang-Rae, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Hang-Rae Kim, PhD, DVM

• Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Dong Ki Kim, MD, PhD

Background

IgA nephropathy (IgAN) has difficulty in explaining the heterogeneity of its clinical presentation and prognosis as the pathogenesis is not completely elucidated yet. We performed transcriptome profiling of peripheral immune cells of IgAN to explore their role in the pathogenesis of IgAN.

Methods

Peripheral blood mononuclear cells were obtained from 20 IgAN patients and 9 healthy controls. The cells were sorted into B, CD4 T, and CD8 T subsets. Single cell RNA sequencing was performed with NovaSeq6000. The patients were categorized according to the eGFR and proteinuria value. The differentially expressed genes (DEG) were identified. Then, gene ontology analysis was done with ToppGene Suite.

Results

After quality control, 32,742 B cells, 101,637 CD4 T cells, 63,029 CD8 T cells were retained for analysis. Cell clusters were presented in UMAP. (Figure 1) Ninety five genes were commonly upregulated in all subsets of IgAN, including AKT1, JUN and TGFB1. (Figure 2) Compared to control group, severe IgAN group exhibited significant increase in DEG expression; 40, 148, 132 upregulated and 233, 77, 78 downregulated DEGs in B, CD4 T, CD8 T cell subsets, respectively. Downregulated DEGs in B subset were highly enriched in MHC protein complex and antigen binding pathway.

Conclusion

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 and it may contribute to the investment of the disease specific biomarkers of IgAN.

Fig 1. Cell cluster annotation

Fig 2. Gene network analysis results

Funding

• Government Support – Non-U.S.