High nephritogenicity of monoclonal antibodies belonging to IgG2a and IgG2b subclasses in rat anti-GBM nephritis.
BACKGROUND
To examine a subclass-effect relationship and a dose-effect relationship of autoantibodies in the rat antiglomerular basement membrane (GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) model, we injected homologous monoclonal antibodies against the NC1 domains of rat type IV collagen into inbred Wistar-Kyoto (WKY) rats.


METHODS
Eight different autoantibodies from each of the IgG1, IgG2a, and IgG2b subclasses were established and administered to groups of four WKY rats at a dose of 300 microg/rat. To examine the dose-effect relationship, we administered 0 to 300 microg/rat of autoantibodies from each subclass to rats.


RESULTS
All IgG1 antibodies induced mild nephritis, whereas the IgG2a and IgG2b antibodies induced moderate to severe nephritis. Some IgG2a and IgG2b antibodies induced pulmonary hemorrhage as well. These antibodies were reactive with alpha3(IV)NC1, alpha4(IV)NC1, or alpha5(IV)NC1. The minimum dose of antibody required to induce nephritis was 30 microg/rat for IgG1, 3 microg/rat for IgG2a, and 1 microg/rat for IgG2b. At doses of 30 microg/rat or less, antibody deposition was generally restricted to the GBM. At doses of 100 microg/rat or greater, antibody deposition extended to both the GBM and tubular basement membrane (TBM). Pulmonary hemorrhage was observed only when a large amount of pulmonary hemorrhagic antibody was administered.


CONCLUSIONS
The severity of nephritis was dependent on both subclass and dose of autoantibodies. It becomes clear that pulmonary hemorrhage in anti-GBM nephritis is induced by autoantibodies.
Kohda
Takayuki
T
Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan.
Okada
Shin-Ichi
S
Hayashi
Atsushi
A
Kanzaki
Susumu
S
Ninomiya
Yoshifumi
Y
Taki
Masafumi
M
Sado
Yoshikazu
Y
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D024141:Collagen Type IV / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D006470:Hemorrhage / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology; D017434:Protein Structure, Tertiary; D051381:Rats; D011921:Rats, Inbred WKY; D012720:Severity of Illness Index
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D024141:Collagen Type IV; D007074:Immunoglobulin G