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Kidney Week

Abstract: FR-PO676

Characteristics of Kidney Resident IgA Antibody-Secreting Cells in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Makita, Yuko, University Health Network, Toronto, Ontario, Canada
  • Haniuda, Kei, University of Toronto, Toronto, Ontario, Canada
  • Murphy, Julia M., University Health Network, Toronto, Ontario, Canada
  • Mak, Martin L., University Health Network, Toronto, Ontario, Canada
  • Suzuki, Yusuke, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Crome, Sarah Q., University Health Network, Toronto, Ontario, Canada
  • Gommerman, Jennifer, University of Toronto, Toronto, Ontario, Canada
  • Reich, Heather N., University Health Network, Toronto, Ontario, Canada
Background

The trigger and sources of pathogenic IgA in IgAN are not established. Prevailing theories suggest that circulating polymeric nephritogenic IgA is produced by either antibody secreting cells located within the mucosa-associated lymphoid tissue or the bone marrow. Our recent work demonstrated that in experimental IgAN mice (BAFF-Tg), mucosal pathobiont-directed IgA antibody secreting cells (APC) are identified within the kidney. In the current study we aimed to characterize kidney IgA APC in experimental IgAN, and to elucidate the factors that foster migration to and residence within the kidney and explore cell-cell interactions within the kidney niche.

Methods

Flow cytometry was used to identify IgA APC in the kidneys of the male BAFF-Tg and C57/BL6 (WT). Single-cell mRNA sequencing (scRNA-seq) was performed in 4 BAFF-Tg and 4 WT at 20 weeks of age to characterize immune cells within the kidney.

Results

We identified an age-dependent increase in IgA-producing plasma cells (PC) by flow cytometry (CD45+, B220-, CD98+, IRF4+, IgA+) within the kidneys of BAFF-Tg but not WT mice; these PC were detectable at 6 weeks of age, and numbers continued to rise by 20 weeks of age. scRNA-seq confirmed a population of IgA APC in the BAFF-Tg kidneys. Analysis of differential gene expression supported phenotypically different subpopulations of IgA APC in kidneys of BAFF-Tg. Ligand-receptor pair analysis suggests cell-cell interaction patterns between IgA APC, macrophages and endothelial cells that may support migration of IgA APC and proliferation of these cells within the kidney.

Conclusion

Our mouse data support the concept that pathogenic IgA production in experimental IgAN can occur within the kidney. We have confirmed the age-dependent presence of IgA-producing PC within the kidneys of the BAFF-Tg by flow cytometry and these cells may be initially proliferating within the kidney. We have further characterized the immune cell populations within the kidney in experimental IgAN using scRNA-seq, and identified possible cell-cell interactions that may foster the migration and support of mucosal derived IgA APC within the kidney, potentially resulting in kidney pathology. Elucidation of the ligands and receptors involved in kidney IgA APC migration and residence will inform therapeutic interventions for the treatment of IgAN.