asialo-gm1-ganglioside and Motor-Neuron-Disease

Topics: Alzheimer Disease; Biomarkers; G(M1) Ganglioside; Guillain-Barre Syndrome; Hematologic Tests; Humans; Motor Neuron Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Specimen Handling

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.

Topics: Antibodies, Monoclonal; Autoimmune Diseases; Diaphragm; Epitopes; Femoral Nerve; G(M1) Ganglioside; Ganglia, Spinal; Gangliosides; Humans; Immunoglobulin M; Motor Neuron Disease; Nerve Tissue Proteins; Organ Specificity; Peripheral Nerves; Polyradiculoneuropathy; Spinal Cord; Spinal Nerve Roots

We tested monoclonal IgM anti-GM1 and asialo-GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysaccharides (LPS) from three stains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme-linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo-GM1, or blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti-GM1 or anti-asialo-GM1 antibodies cross-react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti-GM1 antibodies.

Topics: Antibodies, Monoclonal; Arachis; Campylobacter jejuni; Cholera Toxin; Cross Reactions; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Glycolipids; Humans; Immunoglobulin M; Lectins; Lipopolysaccharides; Motor Neuron Disease; Paraproteinemias; Peanut Agglutinin; Plant Lectins; Species Specificity

A 31-year-old man had noticed slowly progressive weakness in his right upper limb girdle. On admission at age 32, fasciculation and muscle atrophy were observed in the right pectoralis major muscle. There was mild muscle weakness in the right triceps brachii muscle. The deep tendon reflexes were normal and the pathologic reflexes were absent. Sensory and autonomic nerve functions were intact. Needle EMG showed fibrillation potentials and positive sharp waves in the right pectoralis major, infraspinatus, extensor carpi radialis, extensor digitorum muscles, the bilateral sternocleidomastoideus and triceps brachii muscles. Motor nerve conduction studies revealed normal conduction velocities and distal latencies as well as no evidence of conduction block or abnormal temporal dispersion. Serum immunoelectrophoresis failed to detect an M protein. Thin-layer chromatography with immunostaining revealed that the serum contained auto antibodies which reacted with asialo-GM1, GM1 and LM1. This case must belong to "proximal lower motor neuron syndrome" proposed by Pestronk et al.

Topics: Adult; Autoantibodies; G(M1) Ganglioside; Gangliosides; Humans; Male; Motor Neuron Disease

We treated five consecutive patients with multifocal motor neuropathy (MMN) with high-dose intravenous immunoglobulin (IVIg). Four patients had increased levels of anti-asialo-GM1 IgM and two of anti-GM1 IgM as well; one patient had no reactivity. We treated them twice with 0.4 g/kg IVIg for 5 consecutive days at a 2-month interval, followed by maintenance infusions up to 6 to 12 months. All patients with high anti-asialo-GM1 had a consistent clinical improvement starting 3 to 10 days after the first IVIg course; in one patient, recovery was complete and persistent for 12 months without additional treatment, while in three patients, improvement only lasted 20 to 30 days. There was a similar improvement in these patients after the second course of IVIg which was maintained by periodic 2-day IVIg infusions. Clinical improvement in these patients was associated with a reduction of conduction block in most, but not all, motor nerves, while antibody titers were not consistently modified by treatment. There was no clinical or electrophysiologic improvement in the patient without antiglycolipid activity after 6 months of IVIg. IVIg may be a safe and effective therapy for MMN.

Topics: Adult; Autoantibodies; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Middle Aged; Motor Neuron Disease; Neural Conduction