title: Induction of Goodpasture antibodies to noncollagenous domain (NC1) of type IV collagen in mice by idiotypic manipulation.
abstract: The characteristic pathogenic autoantibodies in Goodpasture's syndrome (GPS) are directed to the noncollagenous domain (NC1) of basement membrane type IV collagen. To examine whether immunization with anti-NC1 antibodies could lead to GPS-like pathology, naive BALB/c mice were immunized intradermally with a mouse IgG anti-NC1 monoclonal antibody or IgG serum fraction derived from patients with GPS. Mice immunized with normal mouse or human IgG and nonimmunized mice served as controls. Anti-NC1 antibodies of IgG isotype were detected in the sera of mice injected with anti-NC1 antibodies, but not in the sera of control mice. The presence of circulating anti-NC1 antibodies coincided in some of the mice erythrocyturia or proteinuria and pathological changes in the kidneys. No pathologic alterations were seen in the control mice. The results show that specific idiotypic manipulation can induce anti-NC1 antibodies and pathological changes resembling human GPS.
authors.affiliation: Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: B
authors.initials: B
authors.lastname: Gilburd
authors.forename: M
authors.initials: M
authors.lastname: Hojnik
authors.forename: M
authors.initials: M
authors.lastname: Damianovich
authors.forename: S
authors.initials: S
authors.lastname: Hacham
authors.forename: Y
authors.initials: Y
authors.lastname: Kopolovic
authors.forename: P
authors.initials: P
authors.lastname: Polak-Charcon
authors.forename: I
authors.initials: I
authors.lastname: Goldberg
authors.forename: A
authors.initials: A
authors.lastname: Afek
authors.forename: L
authors.initials: L
authors.lastname: Hun-Chi
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001324:Autoantigens / Q000008:administration & dosage; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology*; D024141:Collagen Type IV; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; C057112:type IV collagen alpha3 chain; D003094:Collagen