Decreased anionic groups and increased permeability precedes deposition of immune complexes in the glomerular capillary wall.
To verify whether an increase in glomerular permeability precedes the deposition of immune complexes in the capillary wall, the following were studied in mice with lupus nephritis: 1) urinary proteins; 2) glomerular transfer of IgG, albumin, and anionic ferritin (AF) (isoelectric point, 4.2-4.6); and 3) anionic groups of the capillary wall as detected by binding of cationized ferritin (CF) (isoelectric point, 7.5-8.6). The glomeruli were investigated by immunofluorescence, immunoelectron, and transmission electron-microscopic studies. Urinary proteins were quantitated and characterized by electrophoresis. When mice were 5 months of age, (the time at which pathologic proteinuria was first detected), immune deposits were few and were confined to the mesangium. Although AF molecules were largely retained at the level of the lamina rara interna, focal leakage of albumin and IgG was detected across capillary walls that were not found to contain immune deposits. Focal and irregular loss of anionic groups, reflected by decreased binding of CF molecules, occurred in the laminae rarae of the basement membrane. Foot processes of glomeruli incubated with CF showed no loss of polyanion. We conclude that the increase in glomerular permeability that precedes deposition of immune complexes is due, in part, to focal loss of anionic groups of the basement membrane.