Autologous immune complex nephropathy. I. Sequential study of immune complex deposition, ultrastructural changes, proteinuria, and alterations in glomerular sialoprotein

Abstract

Experimental evidence suggests that barriers to glomerular filtration of macromolecules exist at the glomerular basement membrane itself and at the level of the epithelial cell and epithelial slit pores. The distribution of negatively charged glomerular sialoprotein (GSP) at the latter site and the reduction in histochemical staining for GSP reported in several clinical and experimental glomerular diseases suggest a role for this material in the regulation of glomerular permeability. Alternatively, reductions in GSP associated with proteinuria may reflect only epithelial cell swelling consequent to the proteinuria. The sequence of subepithelial immune complex deposition, epithelial cell swelling and foot process fusion, alterations in histochemical staining for GSP, and development of proteinuria was studied in 12 Lewis rats biopsied weekly during development of autologous immune complex (Heymann) nephropathy. Deposition of IgG was detectable 3 weeks after antigen injection by immunofluorescence. Electron-dense deposits were first seen by electron microscopy coincident with the appearance of complement at week 4. Proteinuria began at 6 to 8 weeks, 3 to 5 weeks after detectable immune complex deposition. Proteinuric animals had marked subepithelial immune complex deposition and extensive epithelial cell swelling and foot process fusion. Despite these changes, there was no detectable reduction in staining for GSP until week 14, 6 to 8 weeks after onset of proteinuria. Reductions in GSP apparently do not play a role in altering glomerular permeability early in autologous immune complex (Heymann) nephropathy, and proteinuria and epithelial cell swelling can be present in this model without detectable changes in GSP. These findings suggest that early alterations in GSP reported in some other proteinuric disorders may be of pathogenetic significance rather than simply a reflection of changes in epithelial cell morphology secondary to proteinuria. In this experimental model of membranous nephropathy, immunofluorescence was more sensitive than electron microscopy in the early detection of immune deposits.