Abstract: SA-PO0718
Single-Cell Transcriptomic Analysis of Terminal Ileum and Peripheral Blood Identifies B Cell Maturation Antigen (BCMA) as a Therapeutic Target in IgAN
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Zhang, Yuemiao, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Wang, Lan, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Wu, Junze, State Key Laboratory for Conservation and Utilization of Bio-resource and School of Life Sciences, Yunnan University, Kunming, China
- Wan, Na, State Key Laboratory for Conservation and Utilization of Bio-resource and School of Life Sciences, Yunnan University, Kunming, China
- Liu, Xingzi, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Lin, Miaomiao, Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital; Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
- Zhou, Xujie, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Liu, Lijun, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Shi, Sufang, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Lv, Jicheng, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Zhang, Zijie, State Key Laboratory for Conservation and Utilization of Bio-resource and School of Life Sciences, Yunnan University, Kunming, China
- Li, Chunmei, State Key Laboratory for Conservation and Utilization of Bio-resource and School of Life Sciences, Yunnan University, Kunming, China
- Cheng, Rui, State Key Laboratory for Conservation and Utilization of Bio-resource and School of Life Sciences, Yunnan University, Kunming, China
- Zhang, Hong, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
Background
IgA nephropathy (IgAN) is associated with dysregulation of the gut mucosal immune system; however, the underlying mechanisms are not yet fully understood, and there is a lack of effective therapeutic targets.
Methods
We performed single-cell RNA sequencing on paired terminal ileum (including epithelium and lamina propria) and peripheral blood from five IgAN patients and five healthy controls to characterize the immune landscapes. Flow cytometry was conducted on peripheral blood from IgAN patients and control groups to validate B cell subset alterations.
Results
Eight major cell types were identified, showing dynamic changes in cell abundance, gene expression, developmental trajectories, and intercellular communication. IgAN patients exhibited increased naïve B cells and IgA+ plasma cells in the terminal ileum, along with higher gut-derived IgA+ plasmablasts in peripheral blood compared to controls. We identified BCMA as a critical survival factor for IgA+ plasma cells, with its ligands APRIL and BAFF markedly upregulated in IgAN patients. Cellular interaction highlighted critical role of T cells and myeloid cells in driving dysregulated B cell responses.
Conclusion
These underscore hyperactivity of IgA+ plasma cells in gut mucosa and suggest BCMA as a potential therapeutic target to reduce excessive IgA production in IgAN.
A: Study design. B-C: 8 celluar subtypes and tissue preference across EP, LP and PBMC. D-E: 5 B cell subtypes and distribution variations across tissues. F: Expression pattern of BCMA, BAFFR ,TACI, APRIL and BAFF. G: B cell subtype proportion between IgAN patients, non-IgAN patients and HCs.
Funding
- Clinical Revenue Support