The functional affinity and specificity of autoantibodies in animal models of anti-glomerular basement membrane disease.
We studied characteristics of the anti-glomerular basement membrane (GBM) antibody response in three animal models of Goodpasture's disease: treatment of Brown Norway (BN) rats with the polyclonal activator mercuric chloride (HgCl2), and immunization of BN and Wistar Kyoto (WKY) rats with rat GBM. Serial serum samples were obtained over the time course of the models, and anti-GBM antibodies eluted from the kidneys. Functional affinity of the anti-GBM antibodies was measured in a solid-phase ELISA incorporating the mild chaotropic agent diethylamine. Evidence for shared epitope specificity with human anti-GBM antibodies was sought using competition ELISA. As with recent studies in human anti-GBM disease, there was no evidence for affinity maturation of the anti-GBM response in the serum of any of the animal models. Antibodies eluted from the kidneys were of higher functional affinity than serum antibodies only in the HgCl2-treated BN rat. There was no obvious correlation between the functional affinity of the antibodies and the severity of nephritis in the three models. Competition studies between eluted anti-GBM antibodies from the rat models and human anti-GBM antibodies did not provide any evidence for shared epitope recognition. This study provides further information on the extent to which these models reflect the human disease.
Marriott
J B
JB
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, UK.
Qasim
F
F
Reynolds
J
J
Pusey
C D
CD
Oliveira
D B
DB
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D001667:Binding, Competitive; D004123:Dimethylamines / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005921:Glomerulonephritis / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007678:Kidney Glomerulus / Q000276:immunology; D007700:Kinetics; D008627:Mercuric Chloride / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011921:Rats, Inbred WKY
D000906:Antibodies; D001323:Autoantibodies; D004123:Dimethylamines; C051951:antiglomerular basement membrane antibody; D008627:Mercuric Chloride; C034516:dimethylamine