ganglioside--gd1b and Peripheral-Nervous-System-Diseases

Antiglycolipid antibody titers are frequently elevated in the serum of patients with autoimmune neuropathies. Some antibodies may be involved in the pathogenesis because glycolipids are surface antigens in the nervous system. Sensory ataxic neuropathy was induced in rabbits sensitized with GD1b ganglioside, which is localized in the rabbit primary sensory neurons of the larger cytoplasms. Systemic infusion of high-titer anti-GD1b antiserum to rabbits pre-inoculated with adjuvant caused vacuolar degeneration with macrophage infiltration in a few axons in the dorsal column of the spinal cord. Anti-GD1b antibody therefore may cause degeneration in rabbit sensory neurons with central axons extending to the dorsal column. Investigations on the clinical features of GBS patients with monospecific anti-GD1b IgG antibodies showed that the antibodies are associated with sensory disturbance, especially disturbance in the deep sensation, and with primary demyelinating form. GD1b is localized in primary sensory neurons and paranodal myelin in the human peripheral nervous system. Monospecific anti-GD1b IgG antibodies may bind to those regions and be involved in the pathogenesis of sensory disturbance and demyelination. Thus, some antiglycolipid antibodies may determine the clinical features of GBS by binding to the regions where the antigens are localized.

Topics: Animals; Antigens, Surface; Autoantibodies; Autoimmune Diseases of the Nervous System; Gangliosides; Glycolipids; Humans; Immunoglobulin G; Peripheral Nervous System Diseases

To describe clinical features, disease course, treatment response, and sural nerve biopsy findings in a patient with chronic sensory ataxic neuropathy, Binet stage A chronic lymphocytic leukemia, and monoclonal IgMλ paraprotein against ganglioside GD1b. During 9 months of hospitalization at two neurologic centers, the patient underwent serial neurologic examinations, neurophysiologic studies, imaging investigations, extensive laboratory work-up, bone marrow, and sural nerve biopsies. The patient had a severe progressive sensory neuropathy accompanied by motor involvement, dysautonomia, and marked bulbar weakness with preserved ocular movements. Conduction studies were characterized by prolonged F-wave minimal latencies, prolonged distal latencies, reduction of compound motor action potentials, and absence of sensory nerve action potentials. Sural nerve biopsy showed endoneurial edema, axonal degeneration, and regeneration, in the absence of cellular inflammation, macrophagic activation, and B-lymphocyte infiltration; no IgM or complement deposition was detected. Myelinated fibers showed redundant/abnormally thickened myelin, myelin vacuolation, and frank intramyelinic edema with condensed axoplasm. Ultrastructural features included axo-glial detachment, disruption of membrane integrity, and myelin uncompaction. This study shows that monospecific anti-GD1b IgM paraprotein is associated with non-inflammatory nerve damage. We suggest that the loss of myelin and axonal integrity reflects antibody-induced disruption of membrane lipid rafts.

Topics: Ataxia; Autoantibodies; Axons; Gangliosides; Humans; Immunoglobulin M; Male; Middle Aged; Myelin Sheath; Neuroglia; Peripheral Nervous System Diseases

We previously reported experimental sensory neuropathy in rabbit induced by the immunization of ganglioside GD1b. The major pathological change in diseased rabbits was degeneration of primary sensory neurons with central axons extending to the dorsal column of the spinal cord. The loss of primary sensory neurons that mediate proprioceptive sensation prompted us to investigate the expression of trkC in dorsal root ganglia (DRG) because this type of neuron is thought depend mainly on neurotrophin-3-mediated trkC signaling. Northern blotting analysis revealed markedly reduced expression of trkC in DRG of diseased rabbits in acute phase. This result together with the absence of lymphocytic infiltration in DRG of diseased rabbits at any stage suggests the anti-GD1b antibody-mediated downregulation of trkC expression could be one of the pathogenesis of this experimental sensory ataxic neuropathy.

Topics: Animals; Antibodies, Blocking; Ataxia; Blotting, Northern; Down-Regulation; Ganglia, Spinal; Gangliosides; Neurons; Oligonucleotides, Antisense; Peripheral Nervous System Diseases; Rabbits; Receptor Protein-Tyrosine Kinases; Receptor, trkC; Receptors, Nerve Growth Factor; RNA, Messenger

A 60-year-old woman was admitted to our hospital with bilateral weakness of the lower limbs. She had been suffering from spastic paraparesis of unknown origin for 12 years since she was 48. Myelopathy with the Th6 level appeared when she was 52 and underwent gradual deterioration. On admission, she showed spastic paraparesis and myelopathy with the Th6 level. A thoracic spinal MRI examination revealed a wholly thin spinal cord. EMG demonstrated that the conduction velocity of the peroneal nerve was 37.8m/sec, and F waves were not evoked on stimulation of the peroneal nerve. Although the anti-GM1 and anti-GD1b antibody titers in the serum were increased on admission, their values decreased transiently after whole plasmapheresis. There was accompanying impairment of the radiculoneuropathy and myelopathy. It is important to measure the titers of anti-ganglioside antibodies in patients with myeloradiculoneuropathy of unknown origin, and whole plasmapheresis is considered to represent a useful treatment for this type of illness.

Topics: Autoantibodies; Female; G(M1) Ganglioside; Gangliosides; Humans; Middle Aged; Peripheral Nervous System Diseases; Plasmapheresis; Spinal Cord Diseases; Spinal Nerve Roots

Topics: Ataxia; Autoantibodies; Autoantigens; Autoimmune Diseases; Ganglia, Sensory; Gangliosides; Glycolipids; Humans; Peripheral Nervous System Diseases

Three of six rabbits immunized with purified GD1b developed ataxic sensory neuropathy. They laid on the floor with their limbs splayed out, and their movements were awkward; but muscle power, tonus, and superficial sensation appeared to be intact. Sciatic nerve motor conduction studies were normal. Axonal degeneration was present in the dorsal column of the spinal cord, in the dorsal roots, and in the sciatic nerve. Some of the nerve cell bodies in the dorsal root ganglia had degenerated and disappeared. No demyelinative lesions or mononuclear cell infiltrations were seen in those regions. No pathological changes were present in the other three immunized rabbits that showed no clinical symptoms. Control rabbits inoculated only with adjuvants showed neither clinical symptoms nor pathological changes. Anti-GD1b antibody was raised in the sera from all six rabbits immunized with GD1b. The monoclonal anti-GD1b antibody GGR12 immunostained about one-half the rabbit primary sensory neurons. Sensitization with GD1b, therefore, may cause ataxic sensory neuropathy in rabbits due to antibody-mediated damage to the primary sensory neurons.

Topics: Animals; Ganglia, Spinal; Gangliosides; Immunization; Motor Activity; Neural Conduction; Neurons, Afferent; Peripheral Nervous System Diseases; Rabbits; Sciatic Nerve; Spinal Cord

A 79-year-old man with sensory dominant polyneuropathy, cerebellar ataxia, and palatal myoclonus had serum IgM M-protein that specifically bound to GM1, GD1b, and asialo-GM1. IgM with the same specificity was detected in his cerebrospinal fluid. Results of immunohistochemical studies showed specific binding of this monoclonal IgM to the cerebellar granular layer, dentate nucleus, inferior olive, and gray matter of the cerebrum and spinal cord. Monoclonal antibody GGR12, monospecific to GD1b, had an immunostaining distribution similar to that of the patient's IgM M-protein. The binding of M-protein may be associated with the development of cerebellar ataxia and palatal myoclonus in this patient.

Topics: Aged; Antigens, Tumor-Associated, Carbohydrate; Cerebellar Ataxia; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Immunohistochemistry; Male; Myelin Proteins; Peripheral Nervous System Diseases