A monoclonal DNA-binding autoantibody causes a deterioration in renal function in MRL mice with lupus disease.
Two DNA-binding monoclonal antibodies (MoAb) derived from lupus mice were examined for their effects on kidney function. Antibody IV-228, reactive with single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) significantly altered kidney function in some MRL/Mp-lpr/lpr (MRL/lpr) mice with lupus glomerulonephritis. Antibody II-410, preferentially reactive with dsDNA, did not modify kidney function in MRL/lpr mice. Neither antibody affected normal healthy MRL/Mp- +/+ (MRL/n) mice. Not all MRL/lpr mice were equally affected by IV-228 and in some animals with clinical disease it was without effect even when high circulating antibody levels were maintained by five sequential daily injections. Its affects upon kidney function appeared to be related to its ability to localize in vivo in glomeruli. It is assumed that epitopes on trapped immune complexes are immunologically available to circulating antibodies, and in those animals where injected antibody is not captured this is because the antigen epitope is either absent or is masked by the animals' own auto-antibodies. We conclude that antibodies which bind to ssDNA contribute to lupus nephritis; that individual mice make DNA-binding antibodies of different fine specificity; and that kidney disease is not always due to the same balance of antibodies in members of a genetically homogeneous stock.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D004247:DNA / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D004277:DNA, Single-Stranded; D004247:DNA