Experimental IgA nephropathy induced by oral immunization.

Abstract

To test the hypothesis that IgA nephropathy can result from a mucosal immune response, mice were orally immunized with one of three protein antigens for 14 wk. Such mice exhibited an essentially pure mucosal antibody response characterized by specific IgA-producing plasma cells in exocrine sites and specific IgA antibodies in serum. Furthermore, 73% of immunized mice had IgA and 88% had immunogen deposited in the glomerular mesangium, and 64% of immunized mice examined ultrastructurally had electron-dense mesangial deposits. All three were present concurrently in 57% of the immunized mice. No differences in regard to IgG or IgM were observed between immunized and control mice for any of these parameters. Mucosal immunization therefore can result in a specific immune response that leads to mesangial deposition of immune complexes containing IgA antibody. In its fundamental features the experimental renal lesion resembles that seen in the human disease IgA nephropathy.

Development of immune-complex glomerulonephritis in athymic mice: T cells are not required for the genesis of glomerular injury

“…23 Indeed, among the murine models of IgAN, those with hematuria and glomerular dysfunction are typically the ones with mesangial complement deposition; [23][24][25][26] conversely, those without complement generally have normal glomerular function. [27][28][29] However, in the system described herein, a pathogenic role for the complement system is improbable, since hematuria occurred even in mice with little or no glomerular C3 deposits.…”

Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies.

“…This hypothesis has gained further support from recent studies demonstrating elevated levels of CIC that contain IgA not only in patients with primary IgA NP (14)(15)(16)(17)(18)(19)(20), but also in patients with Henoch-Schoenlein purpura (16,(21)(22)(23), dermatitis herpetiformis (23,24), and IgA NP associated with liver cirrhosis (25,26). In rodents, IgA-containing CIC either infused (27) or induced by enteral (28) or parenteral (29) immunization with defined antigens can deposit in the mesangium and initiate a proliferative glomerulonephritis similar to that observed in humans. Despite this, attempts to isolate a specific IgA-CIC-associated antigen in humans have been unsuccessful and the pathogenic role of these CIC remains elusive.…”

Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy

“…The onset of macroscopic hematuria shortly after an upper respiratory or intestinal tract infection frequently heralds the clinical manifestations. Furthermore, extended feeding of mice with dietary proteins leads to their mesangial deposition, accompanied by IgA [14] . Collectively, these findings suggested that exogenous antigens of microbial or food origin may play an essential role, as components of CIC, in the pathogenesis of IgAN.…”