Characterization of anti-GBM antibodies involved in Goodpasture's syndrome.
Goodpasture's syndrome is a life threatening autoimmune kidney disease. The patients have autoantibodies to the glomerular basement membrane, which are specific for the C-terminal domain of type IV collagen (NC1). The major antigen has been localized to the alpha 3 (IV)-chain. We have investigated sera from 44 patients with anti-NC1 antibodies. The quantity of antibodies to four different alpha(IV)-chains of type IV collagen was measured with direct ELISA. We used affinity chromatography to separate the antibodies and their specificities were studied with ELISA. The results show that about 1% of the patients total IgG are anti-NC1 antibodies and that 90% of these antibodies are specific for the alpha 3(IV)-chain. Antibodies to the other alpha(IV)-chains were found in 80% of the patients. Furthermore, affinity purified anti-alpha 3(IV) antibodies from one patient were inhibited by antibodies from the other patients, from 4 to 72%. The antibodies, from 39 of the patients, were inhibited by a monoclonal antibody against the alpha 3(IV)-chain. The results indicate that patients with Goodpasture's syndrome can have antibodies to most of the alpha(IV)-chains, while the majority of anti-NC1 antibodies are restricted to the alpha 3(IV)-chain. Moreover the number of epitopes seems to be limited and the majority of the antibodies from most patients are against one single epitope on the alpha 3(IV)-chain.
Hellmark
T
T
Department of Nephrology, University Hospital, Lund, Sweden.
Johansson
C
C
Wieslander
J
J
D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D001485:Basement Membrane / Q000276:immunology; D002846:Chromatography, Affinity; D003094:Collagen / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D003094:Collagen