Canine and human myasthenia gravis autoantibodies recognize similar regions on the acetylcholine receptor.
Serum from 35 cases of naturally occurring acquired canine myasthenia gravis (MG) were assayed for patterns of autoantibody specificities against canine acetylcholine receptor (AChR) using monoclonal antibodies (mAbs) and antiserum against defined regions of the AChR as competitive inhibitors of autoantibody binding. In human MG patients and in animals immunized with AChR purified from fish electric organs or mammalian muscle, most of the antibodies are directed against the main immunogenic region (MIR), a conformationally dependent region located on the extracellular surface of the alpha subunit away from the ACh binding site. In our studies using canine MG serum, we found that, as in human MG and in animals immunized with AChR, the antibody response is heterogeneous and predominantly IgG, with a large proportion of the autoantibodies directed against the MIR. The mAbs to the MIR blocked an average of 68% of serum antibody binding. A mAb to the beta subunit and polyclonal antiserum to the gamma subunit blocked an average of 34% and 39% of serum antibody binding, respectively, indicating that these subunits also contain relevant antigenic determinants, a pattern that has also been observed in human MG serum. Anti-alpha bungarotoxin binding site antibodies made up only a small fraction of the autoantibody population in canine MG as in human MG. These and other features described here suggest that canine MG is a useful model of human MG.
Shelton
G D
GD
Salk Institute for Biological Studies, San Diego, CA 92138.
Cardinet
G H
GH
Lindstrom
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D004285:Dogs; D006801:Humans; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D014101:Torpedo
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D011950:Receptors, Cholinergic