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Cholinergic neuron-specific ganglioside GQ1bα a possible target molecule for serum IgM antibodies in some patients with sensory ataxia

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Abstract

In neurological diseases the presence of certain anti-glycosphingolipid antibody species is associated with the clinical features. We recently isolated the novel cholinergic neuron-specific gangliosides GQ1bα and GT1aα from bovine brain. A monoclonal antibody specific for GQ1bα and GT1aα reacted strongly with the dorsal horn of human spinal cord but not with human motor neurons. We investigated the serum antibodies to these minor gangliosides in a number of neurologic diseases and found that 4 patients with sensory ataxic neuropathy had a remarkably high IgM anti-GQ1bα antibody titer. GQ1bα may be a target molecule for serum IgM antibodies in some patients with sensory ataxic neuropathy.

Introduction

Certain species of anti-ganglioside antibodies are associated with specific clinical features in a number of neurologic diseases. IgG anti-GQ1b antibody which cross-reacts with GT1a is associated with acute ophthalmoparesis (Chiba et al., 1993; Yuki, 1996). IgG anti-GM1 antibody, which often cross-reacts with GD1b and asialo-GM1, is associated with acute motor axonopathy (Yuki et al., 1990; Kornberg et al., 1994).

We recently isolated the novel cholinergic neuron-specific gangliosides GQ1bα and GT1aα from bovine brain (Ando et al., 1992; Hirabayashi et al., 1992). A monoclonal antibody specific for GQ1bα and GT1aα immunostained the dorsal and lateral horns of human spinal cord, but not the anterior horn (Kusunoki et al., 1993a). GQ1bα and GT1aα are thought to be localized on a certain population of cholinergic neurons. To examine the biological functions of GQ1bα and GT1aα, we investigated the serum autoantibodies to these minor gangliosides that are present in various neurological diseases and whether they are associated with specific clinical features.

Section snippets

Glycosphingolipids

GM1, GM1b, GM1α, GD1b, GT1aα, GT1b, GQ1b and GQ1bα were purified from bovine brain ganglioside mixtures by Q-Sepharose (Pharmacia, Uppsala) column chromatography (Hirabayashi et al., 1992). Sialosyl paragloboside (SPG), sialosyl lactosaminyl paragloboside (SLPG) and sulfated glucuronyl paragloboside (SGPG) were prepared from bovine cauda equina according Ariga et al. (1987). Their structures are shown in Table 1.

Sera

Serum samples were obtained from 99 patients with Guillain-Barré syndrome (GBS), 55

Results

One patient with ASN (patient 1) and 3 with CIDP (patients 2–4) had IgM anti-GQ1bα antibody titers of more than 128,000 (Table 2, Fig. 1). Two GBS patients and 1 FS patient had an IgM anti-GQ1bα antibody titer of 1,000. Three GBS patients, 1 FS patient, 3 CIDP patients, 1 amyotrophic lateral sclerosis patient and 1 normal control subject had IgM anti-GQ1bα antibody titers of 500. The other disease controls and NC subjects had IgM anti-GQ1bα antibody titers of less than 500. In contrast, 1 GBS

Discussion

Four patients with sensory ataxic neuropathy had remarkably high IgM anti-GQ1bα antibody titers. All had high IgM antibodies titers to GD1b, GT1b and GQ1b, but only 1 had high IgM antibody titer to GT1aα. GD1b, GT1b, GQ1b and GQ1bα share a NeuAc α2–8 NeuAc structure that is α2–3 linked to an internal galactose of the gangliotetraosyl core structure. The patients had IgM paraprotein. The result of absorption test suggests that each paraprotein reacted with GD1b, GT1b, GQ1b and GQ1bα. The

Acknowledgements

This research was supported in part by grants-in-aid from Kato Memorial Trust for Nambyo Research, The Japan Medical Association, Tsubaki Memorial Neuroscience Research Foundation and a Research Grant for Neuroimmunological Diseases from the Ministry of Health and Welfare of Japan.

References (13)

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