Induction of proteinuria in the rat by a monoclonal antibody against SGP-115/107.

ABSTRACT

The role of individual antigenic determinants in the pathogenesis of antibody-mediated glomerular injury is, at present, incompletely understood. This study was designed to compare the effect of monoclonal antibodies upon binding to three distinct antigenic determinants present in the glomerular capillary wall. Ten monoclonal antibodies were tested for their nephrotoxic capacity in the rat. Six antibodies directed against basement membrane laminin and three antibodies with specificity for a 129/117 kd antigenic complex present on endothelial and glomerular visceral epithelial cell surfaces did not induce proteinuria or structural injury. A non-complement binding monoclonal antibody that immunoprecipitates a 115/107 kd sialo-glycoprotein (SGP-115/107) from glomerular cell membrane preparations and a 107 kd component from proximal tubules, intestinal cells and liver cells, induces glomerular epithelial cell alterations consisting of focal obliteration of foot process architecture, vacuolar changes in the cytoplasm, microvillous transformation of the cell surface, and focal retraction of podocytes, resulting in detachment of the epithelium from the underlying basement membrane. These structural changes are accompanied by immediate transient proteinuria only in animals given complete Freund's adjuvant at the time of antibody administration. These studies indicate that direct antibody-mediated glomerular injury can be induced in the rat by administration of monoclonal antibodies specific for cell associated antigens.