ganglioside--gd1b and Neuromuscular-Diseases

We followed a patient with a lower motor neuron form of motor neuron disease whose neurologic disorder improved following immunotherapy. The patient did not have an M protein but did have IgM antibodies to ganglioside GM1 detectable at serum titers of 1:2,000 by ELISA. These antibodies were found only in the IgM fraction with lambda light chains and immunoreacted with GD1b and Gal (beta 1-3) GalNAc.

Topics: Adult; Antigens, Tumor-Associated, Carbohydrate; Autoantibodies; Chromatography, High Pressure Liquid; Disaccharides; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Immunotherapy; Male; Motor Neurons; Neuromuscular Diseases

Small amounts of oligoclonal immunoglobulins were detected by Western blotting in the serum from a patient with motor neuron syndrome. The prominent one, a monoclonal IgM lambda, reacted strongly with the gangliosides GM1 and GD1b and more weakly with asialo GM1, as shown by immunoenzymatic staining of thin-layer chromatograms of gangliosides, ELISA on purified glycolipid coats and immunoadsorption with purified GM1. Affinity-chromatography with purified GM1 resulted in the purification of monoclonal IgM lambda. This purified IgM and its Fab fragments showed the same pattern of reactivity with gangliosides as that observed with whole serum. Such monoclonal IgM could be responsible for motor neuron diseases in some patients with overt or barely detectable monoclonal gammopathies.

Topics: Aged; Antibodies, Monoclonal; Autoantibodies; Blotting, Western; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Male; Motor Neurons; Neuromuscular Diseases

Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established.

Topics: Antibodies; Antibody Specificity; Chromatography, Thin Layer; Cross Reactions; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Glycosphingolipids; Humans; Nervous System Diseases; Neuromuscular Diseases; Polyneuropathies

IgM lambda monoclonal antibodies in two patients with motor neuron disease showed the same unique antigenic specificity. They bound to gangliosides GM1 and GD1b and to lacto-N-tetraose-BSA. By immunofluorescence microscopy they bound to central and peripheral nerve tissue and to motor end-plates at the neuromuscular junction. Sera from control subjects did not contain antibodies of similar specificity. Monoclonal IgMs with the same unique specificity could be responsible for motor neuron disease in some patients with monoclonal gammopathies.

Topics: Antibodies, Monoclonal; Autoantibodies; Epitopes; Female; Fluorescent Antibody Technique; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Male; Middle Aged; Motor Neurons; Nerve Tissue; Neuromuscular Diseases; Oligosaccharides

We demonstrated the binding of an IgM monoclonal protein, obtained from a patient with motor neuron disease, with known antibody activity against gangliosides GM1, GD1b, and asialo GM1, to neuromuscular junctions in guinea pig gastrocnemius muscle, using an indirect immunofluorescence technique. Staining disappeared after delipidation of muscle sections. Denervated muscle sections showed no labeling at the neuromuscular junction after incubation with the patient's serum. This indicates presynaptic binding of the IgM M protein and supports the concept that IgM monoclonal antibody to nerve terminal determinants may underlie a motor neuron disorder.

Topics: Animals; Antibodies, Monoclonal; Fluorescent Antibody Technique; G(M1) Ganglioside; Gangliosides; Guinea Pigs; Humans; Immunoglobulin M; Motor Neurons; Neuromuscular Diseases; Neuromuscular Junction; Staining and Labeling

Topics: Animals; Antibody Specificity; Autoantibodies; Epitopes; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Mice; Mice, Inbred Strains; Motor Neurons; Neuromuscular Diseases; Paraproteinemias

IgM monoclonal gammopathy has been reported in some patients with motor neuron disease. The monoclonal IgMs in several of the patients bind to the carbohydrate epitope Gal (beta 1-3) GalNAc, which is shared by gangliosides GM1 and GD1b and glycoproteins in the nervous system and crossreacted with Gal (beta 1-3) GlcNAc. They also immunostain spinal cord and gray matter and presynaptic terminals of motor neurons at the neuromuscular junction. The role and mechanisms of action of these antibodies in motor neuron disease is under investigation.

Topics: Antibodies, Monoclonal; Antibody Specificity; Female; G(M1) Ganglioside; Gangliosides; Glycoconjugates; Humans; Immunoglobulin M; Male; Middle Aged; Motor Neurons; Neuromuscular Diseases

We demonstrated that an IgM M-protein from a patient with motor neuron syndrome had antibody activity against gangliosides GM1, GD1b, and asialo GM1. Studies with a sugar-binding lectin suggested that the epitope in the patient's M-IgM involved the Gal(beta 1-3) GalNAc moiety. Immunohistological techniques demonstrated staining of axons in the lumbar roots, granular cells, and white matter in the cerebellum by the patient's M-IgM. We propose that, in this case, an autoimmune mechanism of motor neuron syndrome associated with a monoclonal protein is most likely.

Topics: Antibodies, Monoclonal; Autoantibodies; Brain; Female; G(M1) Ganglioside; Gangliosides; Humans; Middle Aged; Motor Neurons; Neuromuscular Diseases; Spinal Cord; Syndrome