Abstract: TH-PO035

Dysregulation of Mucosal Immune Response in IgA Nephropathy

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental 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
  • Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

IgA nephropathy (IgAN) is associated with dysregulation of mucosal immune system, which manifests as mesangial IgA deposition leading renal impairment. However, it is not unclear which gut-associated lymphatic tissue (GALT) or nasal-associated lymphoid tissue (NALT) is more involved in the pathogenesis of IgAN. Indeed, the origin of nephritogenic IgA has been obscure. Several studies demonstrated the efficacy of tonsillectomy and corticosteroid therapy, whereas recent NEFIGAN study suggested that 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 GALT in murine IgAN using IgAN-prone “ddY mice”.

Methods

Mesenteric lymph node (MLN) is considered to be a key function of GALT in murine. Levels of aberrantly glycosylated IgA and IgA-IgG immune complexes (IC) in serum and supernatant from cultured MLN and splenocytes were measured using IgAN onset and quiescent ddY mice (each n=15). Level of aberrantly glycosylated IgA was measured by the binding of Sambucus nigra bark lectin and Ricinus communis agglutinin I.

Results

Serum levels of aberrantly glycosylated IgA and IgA-IgG IC in IgAN onset ddY mice were significantly higher than those in quiescent ddY mice (P<0.01). However, there were no significant differences in the levels of aberrantly glycosylated IgA and IgA-IgG IC produced by MLN between IgAN onset and quiescent mice. Serum levels of aberrantly glycosylated IgA and IgA-IgG IC correlated with those in culture supernatant of splenocytes (P<0.05). However, the sugar component of IgA produced by MLN was different from those in circulation in IgAN onset ddY mice. Furthermore, serum IgA-IgG IC levels did not associate with those levels produced by cultured MLN.

Conclusion

Serum levels of aberrantly glycosylated IgA and IgA-IgG IC elevated in IgAN onset ddY mice. Glycosylation pattern of circulatory IgA was different from those originated from GALT. Therefore, IgA originated from GALT did not form immune complexes with IgG. Present study suggested that the GALT may not be involved in the pathogenesis of murine IgAN.

Funding

  • Government Support - Non-U.S.