Rat bovine serum albumin (BSA) nephritis. VI. The influence of chemically altered antigen.

Bovine serum albumin (BSA) used to incite chronic serum sickness glomerulonephritis in rats was chemically modified to study the effect of antigenic alteration. The BSA was used in its native form (n-BSA) as well as anionic (a-BSA), cationic (c-BSA) or glycosylated (g-BSA) forms. Spontaneously hypertensive rats (SHR) preimmunized 8 weeks earlier received daily intravenous injections of the respective BSA preparations for the ensuing 3 weeks. Histological examination of their kidneys revealed that c-BSA given for 2 weeks induced a severe diffuse proliferative glomerulonephritis and profound proteinuria. Electron-dense deposits localized preferentially in the subepithelial spaces of renal glomeruli from these rats, but a few in the mesangia. Quite differently, rats receiving n-BSA or g-BSA developed a less severe form of glomerulonephritis even after 3 weeks of injections. Besides the massive mesangial deposits, the subepithelial deposits were conspicuous in the glomeruli from rats given g-BSA for 2 weeks, but deposition in glomerular capillaries was rare in rats given n-BSA for the same duration. In contrast, the administration of a-BSA resulted in minimal abnormalities visible by light microscopy and a few immune deposits in the mesangia even at the third week. The antibody response in rats given c-BSA or a-BSA was apparently different from n-BSA treated rats. The present study shows the important role of the antigen's electric charge in the pathogenesis of proliferative glomerulonephritis. The foregoing results also foster our proposal that the carbohydrate content of the antigen influences the development of this renal disease.