Abstract: TH-PO0277
Increased Extracellular Matrix of Mesangial Cells in IgAN Is a Pathogenic Change Caused by IgA Deposition
Session Information
- Glomerular Diseases: Cell Biology
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
- JunLi, Wan, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Chen, Qilin, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Li, Shuying, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qiu, Li, Children’s Hospital of Chongqing Medical University, Chongqing, China
Background
Immunoglobulin A nephropathy (IgAN) is a disease characterized by mesangial proliferative glomerulonephritis caused by IgA deposition in the mesangial area, but the molecular characteristics of mesangial cells are still unclear.
Methods
We retrospectively reviewed pediatric nephrotic syndrome (NS) cases with mesangial IgA deposition but otherwise MCD-compatible light/electron microscopy features (MCD-IgAN group). MCD patients without mesangial IgA deposition served as the MCD group, and those with NS-type IgAN (mesangial proliferation) as the NS-IgAN group. Single-cell RNA-sequencing was performed on kidney biopsies from MCD-IgAN (n=1), MCD (n=4), and NS-IgAN (n=3) cases. Differentially expressed genes (DEGs) between groups were identified and validated by immunohistochemistry (IHC). Additionally, a B6-hIGHA1/Cd14-FCAR(CD89) mouse model was generated by knocking in human FCAR(CD89) downstream of the Cd14 sequence together with human IgA1.
Results
The incidence of hematuria in the MCD-IgAN group was significantly lower than that in the NS-IgAN group. Most patients in the MCD-IgAN and MCD groups were steroid-sensitive, while the NS-IgAN group was mostly steroid-resistant. The proportion of steroid-dependence in the MCD-IgAN group showed no statistical difference compared to the MCD group but was significantly higher than that in the NS-IgAN group (P<0.001). The scRNA-seq of kidney biopsy showed that the extracellular matrix-related molecules of mesangial cells in the NS-IgAN group were significantly higher than those in the MCD-IgAN group, represented by FN1. IHC confirmed that FN expression (encoded by FN1) was markedly higher in NS-IgAN kidneys than in MCD-IgAN and MCD kidneys, with no significant difference observed between the latter two. In the B6-hIGHA1/Cd14-FCAR(CD89) mice, hIgA1 was deposited in the mesangium, no obvious proliferative lesions were observed under light microscope, and the expression of FN in the glomerular mesangium was not significantly increased.
Conclusion
Children with MCD-IgAN exhibit a clinical and molecular phenotype resembling that of MCD. The increased extracellular matrix of mesangial cells suggests that IgA deposition has caused pathogenic changes in the glomerular area, and FN may be a potential clinical marker.