Spontaneous glomerulonephritis in rabbits: role of a glomerular capillary antigen.

Overt glomerulonephritis, detected by abnormal proteinuria, occurred in 3.3% of young (2.5 kg) male New Zealand White (NZW) rabbits. Histologically, mild to moderate mixed membranous and proliferative glomerulonephritis was observed. Glomerular deposits of IgG and C3 and electron microscopic findings were not typical of circulating immune complex accumulation, nor did they suggest anti-glomerular basement membrane (GBM) antibody. Segmental and less intense glomerular deposits of IgG were found in up to 48% of nonproteinuric NZW rabbits of the same age; histologic changes were minimal. IgG antibodies in sera from proteinuric rabbits or eluted from their kidneys reacted by indirect immunofluorescence with antigens distributed (discontinuously) along the glomerular capillary walls, and in some cases within the walls of small arteries of normal rabbit kidney sections. By indirect immunoperoxidase electron microscopy, the reactive antigens were present at the surfaces of the epithelial cell foot processes where they abut the GBM. This spontaneous glomerulonephritis appears to involve fixation of antibodies to antigens distributed in a discontinuous pattern in the glomerular capillary wall. The mechanism would be much like that causing anti-GBM antibody glomerulonephritis, except that the glomerular antigen is different. Possibly some forms of glomerulonephritis develop in humans as a result of a similar process.