Treatment with antibody reactive with the nephritogenic idiotype, IdLNF1, suppresses its production and leads to prolonged survival of (NZB x SWR)F1 mice.
The F1 progeny of the cross between SWR and NZB mice (SNF1) develop severe immune complex glomerulonephritis, similar to that seen in human SLE. An idiotypically-related family of nephritic antibodies (IdLNF1) has been shown to be important in the pathogenesis of autoimmune glomerulonephritis in these mice. Interestingly, the majority of IdLNF1+ antibodies do not bind DNA. Here, we sought to examine whether regulation of the expression of this idiotype was important in the development of lupus nephritis and to identify the mechanisms regulating its expression. In the present study, biweekly injections of SNF1 mice with 100 micrograms of rabbit anti-IdLNF1 antibodies, beginning at 8 to 10 weeks of age, resulted in significant P < or = 0.05) suppression of IdLNF1+ Ig(G+M) and IgG production. The decrease appeared to be mediated via significant (P < or = 0.05) decreases in the percentage of IdLNF1-expressing B cells and CD4+ IdLNF1-specific T cells in the treated SNF1 mice compared to the controls. This was accompanied by a significant (P < or = 0.005) increase in survival with delayed onset of glomerulonephritis. Surprisingly, there was no difference in the incidence of anti-DNA antibody production between the treated and control SNF1 mice. These results support the hypothesis that dysregulation of pathogenic idiotypes, not confined to anti-DNA antibody idiotypes as had been shown in previous studies, may contribute to the development of SLE.
Uner
A H
AH
Department of Pathology, SUNY-HSC, Syracuse 13210.
Knupp
C J
CJ
Tatum
A H
AH
Gavalchin
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use; D000974:Antibodies, Antinuclear / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000628:therapy; D007105:Immune Complex Diseases / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D051379:Mice; D008806:Mice, Inbred AKR; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D007130:Immunoglobulin Idiotypes