Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney.
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.
Raz
E
E
Department of Medicine, Hadassah University Hospitals, Jerusalem, Israel.
Brezis
M
M
Rosenmann
E
E
Eilat
D
D
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
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; D003165:Complement System Proteins; D004247:DNA