EXPERIMENTAL IgA NEPHROPATHY INDUCED BY ORAL IMMUNIZATION* (1)
An expansion of specific IgA synthesizing cells in mesenteric lymph nodes,spleen,and secretory mucosae and a significant elevation of IgA antibody in serum and exocrine fluids can occur in response to oral immunization.
In both intestines and bronchi the number of specific IgA-producing cells in immunized mice was significantly greater than in non immunized mice. The mean IgA antibody level against the particular immunogenin immunized mice is significantly different from the mean antibody level against the immunogenic non immunized mice or in mice immunized with the other antigens.
There was mesangial accumulation of IgA in 14 of 19 immunized mice, but in only 2 of 15 non immunized control mice. In positive mice the staining among glomeruli was uniform throughout the cortex and deposits were restricted to mesangial areas.
Electron-dense deposits were observed within mesangial and parameningeal sites. Urine from mice studied periodically by placement in metabolic cage revealed sporadic proteinuria but no hematuria in both immunized and control groups,nor could hematuria or proteinuria be consistently demonstrated in any group at the time of killing.
The lack of C3 deposition in glomeruli, histologic changes such as mesangial proliferation or increased matrix,and hematuria/proteinuria are the major differences between this murine model and human disease. Slow deposition of antibody in a chronic time course might limit the positive feedback component of the alternative pathway C3 convertase,thereby limiting complement deposition. Immune complexes containing only IgA antibody fix complement by the alternative pathway but that this complement fixation (in the mouse)is limited to the fluid phase. Although all the IgA deposits in our experiments contained chain, which indicates that at least some of the IgA was dimeric or oligomeric, J chain has not been described in the human disease.