Mapping immunoreactive epitopes in the human peripheral nervous system using human monoclonal anti-GM1 ganglioside antibodies

Abstract

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.

Acute Transverse Myelitis and Acute Motor Axonal Neuropathy Developed after Vaccinations against Seasonal and 2009 A/H1N1 Influenza

“…Moreover, a few cases of ADEM after C. jejuni infection have been reported, and in one case concurrent AMAN was documented (21). Indeed, gangliosides are abundantly found not only in the PNS but also in the CNS (22), and immunohistochemistry analysis showed broad distribution of GM1 across the spinal cord, especially in the grey matter (23). Based on these findings, we speculate that the presence of a common antigen may underlie simultaneous development of ATM and AMAN.…”

The Guillain–Barré syndrome: a true case of molecular mimicry

“…Abbreviations: APC, antigen presenting cell; mø, macrophage; T, T cell. Ganglioside auto-antibodies are neuropathogenic Polyclonal and monoclonal anti-ganglioside antibodies bind to the Schwann cell surface, nodes of Ranvier and axons in peripheral nerves, depending on the specificity of the anti-ganglioside antibodies [31,32]. The isotype and subclass of the anti-ganglioside antibodies indicate that they are able to bind complement and this has indeed been demonstrated [33].…”

Autoantibodies associated with peripheral neuropathy

“…Taken as a whole, studies on the ganglioside composition of peripheral nerves do not reveal an increased content of GM1 in motor nerves that would account for the association of anti-GM1 antibodies with motor nerve disorders. 122 Immunocytochemical studies have suggested that much of the GM1 and cross-reacting glycoconjugates are not readily accessible to antibodies, but do indicate that these antibodies bind to the surface of isolated bovine motor neurons, 22 to nodes of Ranvier, 21,120 and to neuromuscular junctions. 120,163 However, binding of human anti-GM1 antibodies is widespread, including sensory structures, and extends beyond those sites conventionally regarded as pathologically affected in motor nerve syndromes.…”

“…120,163 However, binding of human anti-GM1 antibodies is widespread, including sensory structures, and extends beyond those sites conventionally regarded as pathologically affected in motor nerve syndromes. 120 This suggests that factors other than accessibility of antigen affect pathological outcome.…”