We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW Fl female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory. (J. Clin. Invest. 1990. 85:530-540.) immunoglobulin gene * pathogenic autoantibody * systemic lupus erythematosus
Indirect immunofluorescence with monoclonal antibodies to 6 different idiotypes was used to characterize immunoglobulins deposited in the glomeruli of renal biopsy samples from 32 patients with systemic lupus erythematosus (SLE) and 19 patients with nonlupus immune glomerulonephritis. IdGN2 was present in 75% of the biopsy specimens from SLE patients and in 6% of those from patients with non-lupus nephritis; IdGNl occurred in 38% and 6%, respectively. The other idiotypes were not increased in biopsy samples from patients with SLE. Deposition of IdGN2 was associated with a subendothelial location of Ig and proliferative changes in the glomeruli. In studies of glomerular eluates from 4 immunosuppressed SLE patients, an average of 26% of total Ig and 37% of anti-DNA was composed of IdGN2. Compared with IdGN2-immunoglobulin, IdGN2+ immunoglobulin
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