Key result
Transplantation of hybridoma clones producing anti-gp70 autoantibodies or injection of purified anti-gp70 IgG induced glomerular gp70 deposition and lupus-like nephritis in non-autoimmune mice.
This study provides direct evidence that anti-gp70 autoantibodies are pathogenic and can induce glomerular pathology in non-autoimmune mice.
Anti-gp70 autoantibodies suffice to induce nephritis in mice; leaves open human relevance and therapeutic targeting.
Several strains of mice, including MRL/MpJ mice homozygous for the Fas mutant lpr gene (MRL/lpr mice), F(1) hybrids of New Zealand Black and New Zealand White mice, and BXSB/MpJ mice carrying a Y-linked autoimmune acceleration gene, spontaneously develop immune complex-mediated glomerulonephritis. The involvement of the envelope glycoprotein gp70 of an endogenous xenotropic virus in the formation of circulating immune complexes and their deposition in the glomerular lesions have been demonstrated, as has the pathogenicity of various antinuclear, antiphospholipid, and rheumatoid factor autoantibodies. In recent genetic linkage studies as well as in a study of cytokine-induced protection against nephritis development, the strongest association of serum levels of gp70-anti-gp70 immune complexes, rather than the levels of antinuclear autoantibodies, with the development and severity of glomerulonephritis has been demonstrated, suggesting a major pathogenic role of anti-gp70 autoantibodies in the lupus-prone mice. However, the pathogenicity of anti-gp70 autoantibodies has not yet been directly tested. To examine if anti-gp70 autoantibodies induce glomerular pathology, we established from unmanipulated MRL/lpr mice hybridoma clones that secrete monoclonal antibodies reactive with endogenous xenotropic viral env gene products. Upon transplantation, a high proportion of these anti-gp70 antibody-producing hybridoma clones induced in syngeneic non-autoimmune and severe combined immunodeficiency mice proliferative or wire loop-like glomerular lesions. Furthermore, deposition of gp70 in glomeruli and pathological changes were observed after intravenous injection of representative clones of purified anti-gp70 immunoglobulin G, demonstrating pathogenicity of at least some anti-gp70 autoantibodies.
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Tabata et al. (2000) studied Systemic lupus erythematosus (murine model). Monoclonal anti-retroviral gp70 autoantibodies (hybridoma cells or purified IgG) vs. Control hybridoma cells or anti-SRBC IgG was evaluated on Induction of glomerular pathology and gp70 deposition. Transplantation of hybridoma clones producing anti-gp70 autoantibodies or injection of purified anti-gp70 IgG induced glomerular gp70 deposition and lupus-like nephritis in non-autoimmune mice.
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