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 cl oned from peripheral blood lymphocytes of patients with multifocal mot or neuropathy and Guillain-Barre syndrome. In solid-phase immunoassay, the antibodies react with GM1, and also in differing degrees to the s tructurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we des cribe the binding patterns of six human anti-GM1 antibodies to epitope s 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 juncti ons and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites convent ionally regarded as pathologically affected in anti-GM1 antibody-assoc iated motor nerve syndromes. This undermines a model of disease pathog enesis based solely on antigen distribution. Factors other than the pr esence 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.