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Abstract: FR-PO0861

Single-Cell Transcriptomics Reveals Stage-Associated CD8+ T-Cell Differentiation Signatures in IgAN

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Lee, Soojin, Eulji University Uijeongbu Eulji Medical Center, Uijeongbu-si, Gyeonggi-do, Korea (the Republic of)
  • Kim, Gwanghun, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)
  • Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Ko, Ara, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Cho, Semin, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong-si, Gyeonggi-do, Korea (the Republic of)
  • Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis. It is challenging to identify patients at risk of progression due to its high clinical and immunological heterogeneity. The study aimed to characterize immune cell alterations according to the different disease stages, with a particular focus on CD8+ T-cell differentiation signatures in early-stage IgAN.

Methods

We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 17 biopsy-proven IgAN patients and 9 healthy controls. The patients were stratified into early and late-stage groups according to estimated glomerular filtration rate and urine protein-to-creatinine ratio. Integrated analyses were also conducted with flow cytometry, branch-level trajectory analysis and pseudobulk pathway analysis.

Results

Single-cell transcriptomic and integrated analysis with flow cytometry revealed stage specific redistribution of CD8+ T-cell subsets (Figure 1). Early-stage IgAN was characterized by enrichment of IL-7Rahigh and IL-7Ramed effector memory CD8+ T cells, whereas late-stage disease showed enrichment of IL-7Ralow subsets. Branch-level pathway analyses revealed coordinated transcriptional programs, with immune activation in early-stage and cytotoxic differentiation in late-stage disease. In contrast, CD4+ T cells, B cells, and NK cells exhibited minimal stage-dependent alterations.

Conclusion

The present study demonstrated stage specific redistribution of CD8+ T-cell subsets and pathway-level immune remodeling differentiation in IgAN. The transition from active immune status to cytotoxic differentiation highlights the insight into the immune landscape in IgAN. This immunological alterations in IgAN may provide clues into disease progression and support future approaches to risk stratification and therapeutic targeting.

Acknowledgment

The present study was supported in part by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2021R1A2C2094586) and SNUH Research Fund (0320213070) to D.K. Kim. The Biospecimens and data used for this study were provided by the Biobank of Seoul National University Hospital, a member of the Korea Biobank Network.

Funding

  • Government Support – Non-U.S.