Experimental autoimmune antiglomerular basement membrane antibody-induced glomerulonephritis. I. The effects of injecting sheep with human, homologous or autologous lung basement membranes and complete Freund's adjuvant.
We compared the effects of injecting human, homologous or autologous lung basement membrane (LBM) and complete Freund's adjuvant into 6-month-old sheep and injecting the same antigens into guinea pigs. All sheep receiving human LBM died of antiglomerular basement membrane (GBM) nephritis by Day 126. They had autoantibodies to antigenic determinants shared by fetal or adult sheep and human LBM and GBM and certain nonvascular basement membranes, but these autoantibodies did not localize in the lung in vivo or cause lung hemorrhages. No sheep injected with homologous or autologous LBM had any evidence of anti-GBM autoantibodies or nephritis or specific lung lesions. Their kidneys are indistinguishable by histologic, immunohistologic, and functional studies from kidneys of age-matched controls. Thus, sheep are very tolerant to their own LBM. Although all guinea pigs developed anti-GBM autoantibodies, they did not get anti-GBM nephritis or specific lung lesions. A hypothesis for the pathogenesis of Goodpasture's syndrome is presented.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage* / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001485:Basement Membrane / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007668:Kidney / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051381:Rats; D012756:Sheep
D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D005620:Freund's Adjuvant