Laboratory Investigation

Kidney International (1982) 21, 36–43; doi:10.1038/ki.1982.6

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

David J Salant1, Michael P Madaio1, Stephen Adler1, Magda M Stilmant1 and William G Couser1

1The Evans Memorial Department of Clinical Research and the Departments of Medicine and Pathology, Boston University Medical Center, and Mallory Institute of Pathology, Boston City Hospital, Boston, Massachusetts

Correspondence: Dr D J Salant, Boston University Medical Center, 80 East Concord Street, Boston, Massachusetts 02118, USA

Received 9 March 1981; Revised 15 June 1981.

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Abstract

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 plusminus 6.7, N = 6; Fab' 9.5 plusminus 2.8, N = 5; normal 1.6 plusminus 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 plusminus 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 plusminus 0.01; Fab' 0.03 plusminus 0.01; IgG 0.17 plusminus 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 perméabilité glomérulaire déterminée par anticorps chez des rats anti-épithélium tubulaire F(ab')2 et Fab'. Les rats été injectés avec des fragments F(ab')2 et Fab' contra anticorps de la bordure en brosse de l'épithélium tubulaire proximal de rat (Fx1A) ont immédiatement une protéinurie [F(ab')2 43,2 plusminus 6,7, N = 6; Fab' 9,5 plusminus 2,8, N = 5; normaux 1,6 plusminus 0,9 mg/d, N = 20] qui persiste pendant 3 à 5 jours. Cela réaction est différent de ce qui est observé chez les rats qui reçoivent l'IgG anti-Fx1A intacte; les rats quelles n'ont pas de protéinurie immédiate (2,2 plusminus 0,3 mg/d, N = 5) quoiqu'à 24 heures la liaison glomérulaire de fragments 125I de l'anticorps soit significativement plus faible que celle de I'IgG intacte [F(ab')2 0,11 plusminus 0,01; Fab' 0,03 plusminus 0,01; IgG 0,17 plusminus 0,01 en % de la dose équimolaire administrée]. Aucune protéinurie n'a été la conséquence de l'administration équimolaire de F(ab')2 et Fab' non-anticorps. Moins de 8% de la protéinurie déterminée par les fragments d'anticorps représentent du matériel injecté et 30 à 38% est de l'albumine. L'immunofluorescence a montré des dépôts faibles et diffus, sur les parois des capillaires giomérulaires, de F(ab')2 et Fab' et le marquage de la bordure en brosse. En électronique, des dépôts denses sous-épithéliaux et l'effacement local des podocytes ont été observés chez les rats qui avaient reçu l'anticorps F(ab')2. La microscopie optique et la coloration par le fer colloïdal n'ont pas montré d'anomalies. Dans notre étude les fragments d'anticorps semblent avoir paroi externe du capillaire glomérulaire et avoir modifié la perméabilité en l'absence de médiateurs connus tels le complément ou les cellules inflammatoires.

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