Epitope specific induction of proteinuria by monoclonal antibodies.
A monoclonal antibody, K9/9, directed against a novel epithelial cell surface sialo-glycoprotein, SGP-115/107, present in the rat glomerulus, has been shown to induce glomerular epithelial cell effacement and retraction, and an increase in protein excretion rate upon in vivo administration. Such damage is not seen upon administration of two additional monoclonal antibodies that recognize this epithelial cell antigen, but with different epitope specificities. To further clarify the mechanism of the epithelial cell abnormality, in vitro studies were performed on glomerular epithelial cells established in primary culture. None of these antibodies alone appeared to induce alterations in the cultured cells. However, an antibody of the IgG2a isotype induced complement-dependent cell damage in vitro, although failed to be pathogenic when administered in the intact animal. The pathogenic potential of K9/9 cannot be attributed to its isotype or rates of association or dissociation from the antigen. Studies suggest that all three monoclonal antibodies recognize different, though spatially close epitopes on SGP-115/107. These results demonstrate, for the first time, a complement- and leukocyte-independent mechanism of tissue injury that results from an epitope-specific interaction between a monoclonal antibody and its specific, epithelial cell surface-antigen. Results obtained in other cell systems suggest that abnormalities of epithelial cell structure and function can result from the interaction between specific cell surface components, particularly growth factor receptors, and monoclonal antibodies that mimic the actions of the specific agonist.
Mendrick
D L
DL
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Rennke
H G
HG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000209:etiology* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes