title: Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney.
abstract: The pathogenesis of SLE is commonly attributed to the deposition of circulating immune complexes consisting of DNA and anti-DNA autoantibodies. However, recent work has shown multiple cross-reactions between anti-DNA antibodies and a variety of cellular and extracellular Ag. To test the possibility that these antibodies interact directly with glomerular Ag and induce kidney dysfunction, we applied mouse and human anti-DNA IgG to the isolated perfused rat kidney. The NZB/NZW mouse monoclonal anti-DNA bound to glomerular Ag with a concomitant induction of proteinuria and a decrease in inulin clearance. The albumin excretion was 2301 +/- 734 micrograms/min at 160 min of perfusion, as compared with 85 +/- 21 micrograms/min in controls (p less than 0.001). The inulin clearance was reduced to 0.17 +/- 0.02 ml/min as compared with 0.28 +/- 0.09 ml/min in controls (p less than 0.05). Polyclonal anti-DNA IgG obtained from patients with lupus nephritis bound to rat glomeruli and induced albumin excretion of 542 +/- 217 micrograms/min at 160 min of perfusion, as compared with 163 +/- 77 micrograms/min in controls (p = NS). The addition of plasma as a source of C to the human IgG increased the proteinuria markedly (albumin excretion of 1115 +/- 195 micrograms/min at 160 min of perfusion, p less than 0.02), probably due to C activation. Preincubation of the reactive mouse and human IgG with DNA completely abolished their binding to renal tissue and its physiologic consequences. These results suggest that direct binding of anti-DNA antibodies to renal Ag may play an important role in the induction of lupus nephritis.
authors: Department of Medicine, Hadassah University Hospitals, Jerusalem, Israel.
authors: E
authors: E
authors: Raz
authors: M
authors: M
authors: Brezis
authors: E
authors: E
authors: Rosenmann
authors: D
authors: D
authors: Eilat
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology*; D001666:Binding Sites, Antibody; D003165:Complement System Proteins / Q000502:physiology; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010477:Perfusion; D010949:Plasma; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; D003165:Complement System Proteins; D004247:DNA