Nephritogenicity of proteoglycans. II. A model of immune complex nephritis.

Antibodies to glomerular basement membrane, heparan sulfate-proteoglycans are nephrotoxic but possess a weak nephritogenic potential. In order to enhance the nephritogenic potential, the antibodies were intravenously administered into rats presensitized with heterologous rabbit IgG. This resulted in the integration of heterologous and autologous phases, the two phases characteristic of the traditional model of nephrotoxic serum nephritis. The presensitization caused a dramatic shift in the binding characteristics of the heterologous antibodies between the kidney and lymphoid tissues. A proliferative form of immune complex glomerulonephritis associated with a remarkable proteinuric response was observed. In addition, a moderate degree of hematuria was noted as well. The proteinuria was largely complement-dependent and may possibly be cell-mediated as well. The proteinuria became severe with increasing production of host IgG antibodies and with their subsequent sequestration in the glomeruli. The predominant glomerular lesions were in the form of epimembranous/subepithelial immune deposits, which became more frequent with timely increasing titer of host autologous IgG antibodies. These findings indicate that antibodies to heparan sulfate-proteoglycan, an authentic component of the basement membrane, are capable of mediating a glomerular injury with acquisition of nephritogenic potential in an appropriate environment of the host. At present, it seems that this is the sole constituent of the basement membrane whose antibodies are capable of inducing an immune complex nephritis.