Experimental IgA nephropathy in rabbits : effects of oral immunization in serum sickness nephritis

Abstract

The mucosal IgA immune system may play a role in the pathogenesis of IgA nephro-pathy. In the first experiment, the author examined whether or not oral administration of bovine gamma globulin (BGG) can induce glomerulonephritis in rabbits. Six rabbits received water alone (Group A) and 6 rabbits received BGG in daily drinking waterr in a 0.1% solution (Group B) for 20 weeks. After 4 weeks, serum IgA antibody and IgG antibody against BGG began to be detectable by ELISA in the orally administered Group B and gradually increased to about 5 times the background amounts in non-administered Group A, but there were no glomerular immune deposits and glomerular damages. In the second experiment, 8 rabbits received intravenous injections of 0.5 mg of BGG once a week (Group C) and 12 rabbits received BGG in daily drinking water in a 0.1% solution (Group D). After 8 weeks, the rabbits in both groups received daily intravenous injection of BGG for 12 weeks and the dose was gradually increased from 0.5 mg to 10 mg. After pre-immunization, serum IgA antibody and IgG antibody against BGG were detectable in all rabbits by ELISA, but the ratio of IgA antibody to IgG antibody in Group D (1.00±0.14: M±SE) was significantly higher than that in Group C (0.41±0.09). At the end of experiment, 7 rabbits in Group D showed mesangial or mesangiocapillary IgA deposits in addition to IgG deposits: they showed mesangial proliferation with small crescents on lightmicroscopy and mesangial electron dense deposits with small subepitherial deposits on electronmicroscopy. On the other hand, 3 rabbits in Group C showed capillary IgG deposits without IgA deposits and little glomerular damages. ELISA for IgA-BGG complex showed elevated serum levels in the rabbits with IgA deposits on glomeruli. These results suggest that oral administration of antigens in serum sickness rabbits induces specific IgA antibody and glomerulonephritis which is similar to human IgA nephropathy.