The pathogenetic role of free-circulating antibody in autologous immune complex glomerulonephritis.

Autologous immune complex glomerulonephritis is an established model of chronic glomerulonephritis which very closely resembles membranous glomerulopathy in man. The disease can be induced in certain rat strains by immunization with tubular brush-border antigen (FxlA) in Freund's complete adjuvant. This procedure is believed to result in circulating immune complexes consisting of anti-FxlA antibody and FxlA antigen, which are deposited along the glomerular basement membrane. Since previous studies have indicated the presence of FxlA antigen in the glomerular basement membrane of normal rat and suggested an in situ formation of immune aggregates at this site as the pathogenetic mechanism in heterologous immune complex glomerulonephritis, the validity of the same mechanism in the pathogenesis of autologous immune complex glomerulonephritis was studied. In an investigation into the pathogenesis of the this model an association was found between the serum titre of autologous anti-FxlA antibody and the presence of immune aggregates in the glomerular basement membrane. Unilateral perfusion of normal kit kidneys with IgG eluted from kidneys of rats with autologous immune complex glomerulonephritis resulted in a binding of autologous anti-FxlA antibody at the subepithelial side of the glomerular basement membrane. These results indicate a pathogenetic role for circulating anti-FxlA antibody and demonstrate that rat anti-FxlA antibody is able to bind to FxlA antigens present in the glomerular basement membrane. Although these experiments do not exclude a possible role for circulating immune complexes, a pathogenetic mechanism of in situ formation of subepithelial immune aggregates in autologous immune complex glomerulonephritis is strongly suggested.