Anti-nuclear antibody production and immune-complex glomerulonephritis in BALB/c mice treated with pristane.
The pathogenesis of systemic lupus erythematosus is thought to be primarily under genetic control, with environmental factors playing a secondary role. However, it has been shown recently that intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) induces autoantibodies typical of lupus in BALB/c mice, a strain not usually considered to be genetically susceptible to the disease. In this study, the induction of autoimmune disease by pristane was investigated. BALB/c mice receiving pristane were tested for autoantibody production and histopathological evidence of glomerulonephritis. Six of 11 mice developed IgM anti-single-stranded DNA antibodies shortly after receiving pristane and 4 developed IgM anti-histone antibodies, but anti-double-stranded DNA antibodies were absent. IgG anti-DNA and anti-histone antibodies were absent. In contrast, the lupus-associated anti-nuclear ribonucleoprotein/Sm and anti-Su autoantibodies produced by these mice were predominantly IgG. In addition to autoantibodies, most of the mice developed significant proteinuria. Light microscopy of the kidney showed segmental or diffuse proliferative glomerulonephritis. Electron microscopy showed subepithelial and mesangial immune-complex deposits and epithelial foot process effacement. Immunofluorescence revealed striking glomerular deposition of IgM, IgG, and C3 with a mesangial or mesangiocapillary distribution. Thus, pristane induces immune-complex glomerulonephritis in association with autoantibodies typical of lupus in BALB/c mice. These data support the idea that lupus is produced by an interplay of genetic and environmental factors and that unlike the MRL or (NZB x W)F1 mouse models, in which genetic susceptibility factors are of primary importance, environmental factors are of considerable importance in the autoimmune disease of pristane-treated BALB/c mice.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006657:Histones / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013729:Terpenes; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004277:DNA, Single-Stranded; D006657:Histones; D011506:Proteins; D017411:Ribonucleoproteins, Small Nuclear; C089635:Su autoantigen; D013729:Terpenes; D055517:snRNP Core Proteins; C009042:pristane