| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Peripheral nerve myelin, especially paranodal myelin, is a target for autoimmune mechanisms in Guillain-Barre syndrome (GBS). It has been reported that glycolipids, including gangliosides, are frequently recognized by antibodies in the acute phase GBS sera. We have reported that ganglioside GD1b is specifically localized in the paranodal myelin and in the primary sensory neurons in human peripheral nervous system. The present investigation showed that electrophysiologically demyelinative changes and sensory disturbances are more common in GBS patients with anti-GD1b IgG antibody than control GBS patients. It indicates that anti-GD1b IgG antibody may bind to paranodal myelin and primary sensory neurons, where GD1b is localized, and cause demyelination and sensory disturbances. GBS patients with IgG antibody against LM1, which is a major ganglioside in human peripheral myelin, showed mild neurological problems and electrophysiologically demyelinative changes. Antibodies against gangliosides that are localized in myelin therefore may be associated not with axonal changes but with demyelination. In rabbits, GD1b is localized in primary sensory neurons but not in paranodal myelin. We have sensitized rabbits with GD1b and induced experimental sensory ataxic neuropathy. In the present investigation we found that anti-GD1b antibody that is not cross-reactive with GM1 may be a crucial pathogenetic factor in this experimental neuropathy. IgG antibodies in sera from GBS patients in the acute phase specifically immunostained rabbit peripheral myelin. A monoclonal antibody produced in mice immunized with rabbit peripheral nerve specifically immunostained rabbit Schwann cells. It is needed to identify the antigen molecules for those antibodies. Those antigens may be useful for inducing animal model of GBS with demyelinative change, leading to understanding pathogenetic mechanisms of GBS and development of effective treatment.
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