High affinity as a disease determinant factor in anti-GM(1) antibodies: comparative characterization of experimentally induced vs. disease-associated antibodies.
Elevated titers of serum anti-GM(1) antibodies of IgG isotype are found frequently in patients with Guillain-Barré syndrome. Much evidence indicates that these autoantibodies are involved in disease progression, but their exact function and the mechanism of their appearance are still unclear. In an attempt to reproduce "ganglioside syndrome", the experimental model of neuropathy developed by Nagai et al. (Neurosci. Lett. 2 (1976) 107), rabbits were intensively immunized with GM(1) in complete Freund adjuvant (CFA). High titers of anti-GM(1) antibodies were produced, with class switch and affinity maturation indicating an elaborate immune response. Unexpectedly, the rabbits did not show any clinical symptoms of neuropathy. Relatively affinities of both IgM and IgG antibodies were significantly lower than those of similar antibodies from neuropathy patients. These results suggest the existence of a threshold value above which affinity of anti-GM(1) antibodies becomes an important factor in disease induction. The absence of neuropathy symptoms in rabbits may be explained by absence of these high-affinity anti-GM(1) antibodies.
Lopez
P H H
PH
Departamento de Química Biológica "Dr. Ranwel Caputto", Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC) and CIQUIBIC, CONICET, Ciudad Universitaria, 5000, Córdoba, Argentina.
Villa
A M
AM
Sica
R E P
RE
Nores
G A
GA
D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D000947:Antigens, Helminth; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D015984:Causality; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology*; D005732:Gangliosides; D006028:Glycosphingolipids / Q000097:blood / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology*; D015801:Helminth Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008565:Membrane Proteins; D015394:Molecular Structure; D010525:Peripheral Nerves / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011485:Protein Binding / Q000276:immunology; D011817:Rabbits
D000947:Antigens, Helminth; D001323:Autoantibodies; C011258:G(A1) ganglioside; C100816:GA1 protein, Haemonchus contortus; D005732:Gangliosides; D006028:Glycosphingolipids; D015801:Helminth Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; C064020:ganglioside GD1alpha; D005677:G(M1) Ganglioside