Abstract: TH-PO0377
Therapeutic Efficacy of Cysteamine Bitartrate in Mouse Model of IgAN
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Yuan, Xiaohan, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Zhang, Yihui, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Li, Huixian, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Liu, Li, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Jin, Qian, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Lu, Wanhong, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Lv, Jicheng, Peking University First Hospital, Beijing, China
- Xie, Xinfang, Xi'an Jiaotong University, Xi'an, Shaanxi, China
Background
Polymeric IgA immune complexes play a critical role in the pathogenesis of IgA nephropathy (IgAN). We previously found that free cysteine-471 in the tailpiece of IgA promoting IgA aggregation, and cysteamine a cystine-reducing agent can dose-dependently reduce IgA complexes in vitro and prevents passive IgA renal deposition in mice. However, its long-term therapeutic effect needs to be further studied.
Methods
To investigate cysteamine's therapeutic effects in IgAN, we established two mouse models of IgA glomerular deposition using humanized IgA1 mice: a chronic IgAN model induced by intraperitoneal Lactobacillus casei cell wall extract and complete Freund’s adjuvant, and a spontaneous IgA deposition model in aged mice. Delayed-release cysteamine bitartrate was given by oral gavage. Circulating total IgA, Gd-IgA1, poly-IgA, and IgA-IgG complexes were measured. Histopathology of the kidney, liver, spleen, and small intestine was evaluated, and bulk RNA sequencing was performed on kidney and liver tissues.
Results
To confirm the therapeutic efficacy of delayed-release cysteamine bitartrate, we first employed an intermittent administration protocol in the chronic IgAN induction model. Circulating immune proteins, including poly-IgA exhibited fluctuations that correlated temporally with cycles of drug administration and withdrawal. Furthermore, both preventive administration and post-disease treatment with cysteamine bitartrate effectively reduced circulating poly-IgA levels, diminished glomerular deposition of IgA and IgM, attenuated macrophage infiltration, and consequently alleviated renal injury. Reduced IgA deposition was also observed in the liver. Dose-response studies revealed that the therapeutic effect of cysteamine bitartrate at 400 mg/kg/d was superior to that at 200 mg/kg/d. In the spontaneous IgA deposition model using aged mice, cysteamine bitartrate significantly lowered circulating poly-IgA levels and decreased glomerular IgA deposition. Bulk RNA sequencing of kidney and liver tissues demonstrated that cysteamine inhibited multiple inflammatory signaling pathways, including the NF-κB signaling pathway.
Conclusion
Collectively, cysteamine bitartrate effectively reduces circulating poly-IgA levels and glomerular IgA deposition in different IgA glomerular deposition models, highlighting its potential as a promising therapy for IgAN.