Altered glomerular permeability induced by F(ab′)2 and Fab′ antibodies to rat renal tubular epithelial antigen

Abstract

Rats injected with F(ab')2 and Fab' antibody fragments directed against an antigen in the rat proximal tubular epithelial brushborder (Fx1A) developed immediate proteinuria [F(ab')2 43.2 +/- 6.7, N=6; Fab' 9.5 +/- 2.8, N=5; normal 1.6 +/- 0.9 mg/day, N=20]), that subsided after 3 to 5 days' duration. This reaction is in contrast to one exhibited by rats given intact IgG anti-Fx1A; the rats that did not develop immediate proteinuria (2.2 +/- 0.3 mg/day, N=5), and the glomerular binding of 125I-antibody fragments was significantly less than that of intact IgG [F(ab')2 0.11 +/- 0.01; Fab' 0.03 +/- 0.01; IgG 0.17 +/- 0.01% administered equimolar dose] at 24 hr. No proteinuria resulted from equimolar doses of nonantibody F(ab')2 and Fab'. Less than 8% of the proteinuria induced by antibody fragments represented injected material, and 30 to 38% was albumin. Immunofluorescence revealed faint and diffuse glomerular capillary wall deposits of F(ab')2 and Fab' and tubular brushborder staining. Subepithelial, electron-dense deposits and focal, podocyte effacement were seen by electron microscopy in rats given the F(ab')2 antibody. Light microscopy and colloidal iron-staining were normal. In our study antibody fragments appear to interact directly with components of the outer, glomerular capillary wall to alter permeability in the absence of recognized mediators such as complement and inflammatory cells.