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

Altered glomerular permeability induced by F(ab′) 2 and Fab′ antibodies to rat renal tubular epithelial antigen. 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 125 I-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, electrondense 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. Modification de la permeabilite glomerulaire determinee par anticorps chez des rats anti-epithelium tubulaire F(ab′) 2 et Fab′. Les rats ete injectes avec des fragments F(ab′) 2 et Fab′ contra anticorps de la bordure en brosse de l'epithelium tubulaire proximal de rat (Fx1A) ont immediatement une proteinurie [F(ab′) 2 43,2 ± 6,7, N=6; Fab′ 9,5 ± 2,8, N=5; normaux 1,6 ± 0,9 mg/d, N=20] qui persiste pendant 3 a 5 jours. Cela reaction est different de ce qui est observe chez les rats qui recoivent l'IgG anti-Fx1A intacte; les rats quelles n'ont pas de proteinurie immediate (2,2 ± 0,3 mg/d, N=5) quoiqu'a 24 heures la liaison glomerulaire de fragments 125 I de l'anticorps soit significativement plus faible que celle de I'IgG intacte [F(ab′) 2 0,11 ± 0,01; Fab′ 0,03 ± 0,01; IgG 0,17 ± 0,01 en % de la dose equimolaire administree]. Aucune proteinurie n'a ete la consequence de l'administration equimolaire de F(ab′) 2 et Fab′ non-anticorps. Moins de 8% de la proteinurie determinee par les fragments d'anticorps representent du materiel injecte et 30 a 38% est de l'albumine. L'immunofluorescence a montre des depots faibles et diffus, sur les parois des capillaires giomerulaires, de F(ab′) 2 et Fab′ et le marquage de la bordure en brosse. En electronique, des depots denses sous-epitheliaux et l'effacement local des podocytes ont ete observes chez les rats qui avaient recu l'anticorps F(ab′) 2 . La microscopie optique et la coloration par le fer colloidal n'ont pas montre d'anomalies. Dans notre etude les fragments d'anticorps semblent avoir paroi externe du capillaire glomerulaire et avoir modifie la permeabilite en l'absence de mediateurs connus tels le complement ou les cellules inflammatoires.