SP163
DYSREGULATED OF MUCOSAL IMMUNITY IN THE PATHOGENESIS OF IGA NEPHROPATHY

INTRODUCTION AND AIMS: Exacerbation of urinary abnormalities are well associated with mucosal infections, such as upper respiratory infection and enteritis. Thus the pathogenesis of IgA nephropathy (IgAN) is closely related with dysregulation of mucosal immune system, which manifests as mesangial IgA deposition leading renal impairment. However, it is unclear which gut-associated lymphatic tissue (GALT) or nasal-associated lymphoid tissue (NALT) is 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 GALT in murine IgAN using IgAN-prone “ddY mice”.

METHODS: Mesenteric lymph node (MLN) is considered to be a key function of murine GALT. Levels of aberrantly glycosylated IgA and IgA-IgG immune complexes (ICs) in serum and supernatant from cultured MLN and splenocytes were measured using IgAN onset and quiescent ddY mice (each n=16). Level of aberrantly glycosylated IgA was measured by the binding of Ricinus communis agglutinin I and Sambucus nigra bark lectin.

RESULTS: In IgAN onset ddY mice, serum levels of aberrantly glycosylated IgA and IgA-IgG ICs were significantly high compared with those in quiescent ddY mice(P<0.05). However, there were no significant differences in the levels of aberrantly glycosylated IgA and IgA-IgG ICs produced by MLN between IgAN onset and quiescent mice. In IgAN onset mice, serum levels of aberrantly glycosylated IgA and IgA-IgG ICs correlated with those produced by splenocytes. However, the glycosylation pattern of IgA produced by MLN was different from those in circulation in IgAN onset ddY mice. Furthermore, serum IgA-IgG ICs levels did not associate with those levels produced by cultured MLN.

CONCLUSIONS: Thus, glycosylation pattern of IgA originated from GALT is different from circulatory IgA in murine IgAN. Present study suggested that the GALT may not be involved in the pathogenesis of murine IgAN.