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Abstract: TH-PO810

Nasal-Associated Lymphoid Tissue Is the Major Induction Site for Nephritogenic IgA in Murine IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kano, Toshiki, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Hitoshi, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Makita, Yuko, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Nihei, Yoshihito, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Fukao, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

The pathogenesis of IgA nephropathy (IgAN) is closely associated with dysregulation of mucosal immune system, which manifests as mesangial IgA deposition leading renal impairment. Several papers reported that Toll-like receptor 9 (TLR9) activated by exogenous pathogens is suspected in aggravation of renal injury in IgAN. However, it is unclear which gut-associated lymphatic tissue (GALT) or nasal-associated lymphoid tissue (NALT) is more involved in the pathogenesis of IgAN. Although the origin of nephritogenic IgA has been obscure, several studies demonstrated the efficacy of tonsillectomy and corticosteroid therapy, whereas the novel targeted-release formulation of budesonide targeting intestinal mucosal immunity reduced proteinuria in IgAN patients. In present study, we focused on the role of NALT and GALT using IgAN-prone ddY mice.

Methods

Levels of aberrantly glycosylated IgA and IgG-IgA immune complexes (IC) in serum and supernatant from cultured cells from NALT, Mesenteric lymph node (MLN) and spleen were measured using IgAN onset and quiescent ddY mice (each n=16) with or without TLR9 ligand (CPG-ODN) stimulation. Level of aberrantly glycosylated IgA was measured by the binding of Sambucus nigra bark lectin (SNA) and Ricinus communis agglutinin I (RCA).

Results

In IgAN onset ddY mice, serum levels of aberrantly glycosylated IgA and IC were significantly higher than those in quiescent ddY mice. However, there were no significant differences in the levels of aberrantly glycosylated IgA and IC produced by MLN between IgAN onset and quiescent mice. Serum levels of aberrantly glycosylated IgA and IC correlated with those in culture supernatant of splenocytes, but SNA and RCA assay revealed that the sugar component of IgA from MLN was different from that in circulatory IgA in IgAN onset ddY mice. The levels of aberrantly glycosylated IgA and IC in NALT and splenocytes were significantly increased by CpG-ODN, however those in MLN were not increased.

Conclusion

Aberrant glycosylation of IgA leading to IC formation was found in cell supernatant from NALT but not in MLN/GALT. The present study suggest that the NALT has a key role in the pathogenesis of murine IgAN