title: Synergistic effects of anti-gp330 and anti-dipeptidyl peptidase type IV antibodies in the induction of glomerular damage.
abstract: Passive Heymann nephritis (PHN) in the rat is induced by the administration of heterologous antibodies to renal tubular epithelium (RTE). The nephritogenic capacity of anti-RTE resides primarily in the antibody fraction directed against a 330-kD glycoprotein (gp330). However, monospecific anti-gp330 antibodies are less nephritogenic than anti-RTE antibodies. This discrepancy led us to study a possible synergizing role for different antibody specificities present within anti-RTE. The enzyme dipeptidyl peptidase type IV (DPP IV) is, like gp330, present in RTE as well as in the glomerulus. Anti-DPP IV antibodies have been shown to induce an acute, transient proteinuria. In this study, we investigated the nephritogenic effect of separate or simultaneous administration of heterologous anti-DPP IV and anti-gp330 antibodies. Injection of anti-DPP IV antibodies resulted in a short-lived glomerular binding, and in a dose-dependent polyuria, albuminuria or proteinuria. Binding of anti-gp330 antibodies was slower, but much more stable. Albuminuria could only be observed in the heterologous phase. Combined injection did not alter antibody-binding kinetics of either antibody nor the albuminuria induced by anti-gp330. However, in the presence of anti-gp330 antibodies, a lower dose of anti-DPP IV was capable to induce transient albuminuria as compared to anti-DPP IV alone. In conclusion, anti-DPP IV and anti-gp330 antibodies bind to different sites in the glomerulus with different kinetics. The presence of anti-gp330 deposits facilitated anti-DPP-IV-induced renal injury.
authors.affiliation: Department of Pathology, University of Leiden, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: van Leer
authors.forename: G M
authors.initials: GM
authors.lastname: de Roo
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoedemaeker
authors.forename: E
authors.initials: E
authors.lastname: de Heer
mesh_terms: D000419:Albuminuria / Q000139:chemically induced; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D003167:Complement Activation; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D026541:Heymann Nephritis Antigenic Complex; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D011141:Polyuria / Q000139:chemically induced; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011917:Rats, Inbred Lew; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4