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Abstract: SA-PO662

Single-Cell Transcriptome Sequencing Identifies New Molecular Markers for Pathogenicity of IgA Deposition in the Mesangial Region

Session Information

  • Pediatric Nephrology - 2
    October 26, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • JunLi, Wan, Children's Hospital of Chongqing Medical University National Clinical Research Center for Child Health and Disorders, Chongqing, Chongqing, China
  • Chen, Qilin, Children's Hospital of Chongqing Medical University National Clinical Research Center for Child Health and Disorders, Chongqing, Chongqing, China
  • Qiu, Li, Children's Hospital of Chongqing Medical University National Clinical Research Center for Child Health and Disorders, Chongqing, Chongqing, China
Background

In a variety of glomerular diseases represented by IgA nephropathy, significant IgA deposition can be seen in the glomerular mesangial area. However, the biomarkers of the pathogenic changes of mesangial cells caused by it are still unclear.

Methods

Children with nephrotic syndrome who had minimal change disease (MCD) with IgA deposition in the mesangial area who were referred to our center in the past 10 years were enrolled as IgA+MCD group. MCD without IgA deposition were enrolled as MCD group. IgAN nephropathy with nephrotic syndrome were defined as NS-IgAN group. The general data, laboratory examination, treatment and follow-up informations of patients were collected and analyzed. Single-cell transcriptome sequencing (scRNA-seq) was performed on renal biopsy tissues. Finally, the findings of scRNA-seq were verified by immunohistochemical staining of renal tissue.

Results

The albumin of all the enrolled patients was less than 30g/L, there was no significant difference between the group IgA+MCD and the group MCD, but they both were lower than that of group NS-IgAN (P<0.05). There was no significant difference in the efficacy of glucocorticoid therapy between group IgA+MCD and group MCD.The analysis of proportion of cell subtypes and the similarity of transcription levels by scRNA-seq of renal biopsy tissue suggested that the transcription level of children with IgA+MCD was similar to that of children with MCD. Comparative analysis of different expression genes in mesangial cells suggested that the expression level of FN1 in children with NS-IgAN was significantly higher than that in children with IgA+MCD. Whether mesangial cells or podocytes, IgAN group was related to molecular characteristics such as extracellular matrix and fibrosis, while other groups were not obvious. Immunohistochemical staining of FN in renal tissue showed that the expression of FN in kidneys of children with NS-IgAN was significantly higher than that of group IgA+MCD and group MCD.

Conclusion

The chilid with IgA+MCD was similar to MCD in clinical features and molecular status of renal tissue. The deposition of IgA in the mesangial region did not cause the increase of extracellular matrix represented by the increase of FN expression and the enhancement of pro-fibrotic function, which meant that the deposition of IgA did not have a pathogenic effect