Mapping immunoreactive epitopes in the human peripheral nervous system using human monoclonal anti-GM1 ganglioside antibodies.
A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GMI, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM I antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.
O'Hanlon
G M
GM
University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland.
Paterson
G J
GJ
Veitch
J
J
Wilson
G
G
Willison
H J
HJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D003964:Diaphragm / Q000276:immunology; D000939:Epitopes / Q000032:analysis*; D005267:Femoral Nerve / Q000276:immunology; D005677:G(M1) Ganglioside / Q000276:immunology*; D005727:Ganglia, Spinal / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D016472:Motor Neuron Disease / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000276:immunology*; D011129:Polyradiculoneuropathy / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology; D013126:Spinal Nerve Roots / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005732:Gangliosides; D007075:Immunoglobulin M; D009419:Nerve Tissue Proteins; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside