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Abstract: SA-PO639

IgA+ Plasma Cells Accumulation in Kidneys of IgA Nephropathy Model Mice and Patients

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Nihei, Yoshihito, Juntendo University, Tokyo, Japan
  • Nakayama, Maiko, Juntendo University, Tokyo, Japan
  • Fukao, Yusuke, Juntendo University, Tokyo, Japan
  • Suzuki, Hitoshi, Juntendo University, Tokyo, Japan
  • Suzuki, Yusuke, Juntendo University, Tokyo, Japan
Background

Previous studies have suggested that nephritogenic IgA are mainly produced in the bone marrow in IgA nephropathy (IgAN), whereas plasma cells (PCs) are often found in the affected kidneys in autoimmune diseases like systemic lupus erythematosus. In the present study, we evaluated the leukocytes in the kidney of IgA nephropathy model mice (gddY mice) and patients and investigated whether PCs infiltrate in the inflamed kidney.

Methods

GddY mice were generated through selectively mating individuals within an early-disease onset group of ddY mice for more than 20 generations. All individual gddY mice exhibit proteinuria and glomerular IgA deposition by 8 weeks of age, followed by obvious renal failure and the pathology being similar to human IgAN. Isolated leukocytes from murine kidney were analysed by flow cytometry. To check whether PCs are present in the patient's kidneys, the kidney biopsy specimens from patients with IgAN were stained with anti-human IgA and CD138 antibodies. To investigate whether the IgA+ PCs in the kidney of gddY mice are generated in T cell-dependent or independent manner, we sequenced the variable region of IgA heavy and light chains from single IgA+ PCs isolated from the kidney of gddY mice.

Results

We found that a significant number of IgA+ PCs accumulated in the kidneys of gddY mice. The IgA+ PCs emerge by 8 weeks of age and further increased with age in gddY mice. Immunohistochemical staining of kidney biopsy samples from IgAN patients revealed the presence of IgA+ PCs cells in the tubulointerstitial region of the kidney. Most of the heavy- and light-chain V region genes from IgA+ PCs in the kidney of gddY mice contained significant numbers of somatic mutations that replaced amino-acids, indicating that these PCs were generated in a T-cell-dependent manner through the germinal center.

Conclusion

We found that IgA+ PCs accumulate in the kidneys of gddY mice and IgAN patients and these IgA+ PCs are generated in T-cell-dependent manner. We will clarify the role of these IgA+ PCs in the pathogenesis of IgAN.