GD1b-specific antibody induces ataxia in Guillain-Barre syndrome

Neurology. 2008 Jul 15;71(3):196-201. doi: 10.1212/01.wnl.0000317093.57106.33.

Abstract

Background: Rabbit ataxic neuropathy and several case reports have suggested a close association of IgG anti-GD1b antibodies with ataxia in Guillain-Barré syndrome (GBS). However, about half of the patients with GBS having IgG anti-GD1b antibodies with no reactivities against other gangliosides (GD1b-mono IgG) do not exhibit ataxia. Antibodies specific to ganglioside complexes (GSCs) containing GD1b have been found in sera from some patients with GBS.

Objective: To investigate whether the reactivities of anti-GD1b IgG to such complexes are different between ataxic and nonataxic patients.

Methods: The authors examined sera from 17 patients with GBS (9 with ataxia and 8 without ataxia) who had GD1b-mono IgG, with the use of an ELISA in which wells were coated with a mixture of GD1b and each of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). The binding activities of the anti-GD1b IgG antibodies against such mixture antigens were compared between ataxic and nonataxic patients.

Results: The reactivities to antigens, such as GD1b combined with GD1a, GT1b, GQ1b, and GalNAc-GD1a, were significantly reduced in ataxic compared with nonataxic patients. Sera from all nonataxic patients had antibody activities to GSCs not containing GD1b.

Conclusions: The addition of another ganglioside may cause conformational change of GD1b. Given the inhibition of the binding ability of the anti-GD1b IgG antibodies by such a conformational change, the anti-GD1b IgG antibodies in ataxic patients may interact closely with GD1b. IgG antibodies highly specific for GD1b may induce ataxia in Guillain-Barré syndrome.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibody Affinity
  • Antibody Specificity*
  • Ataxia / etiology*
  • Ataxia / immunology
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood
  • Autoantibodies / physiology*
  • Binding Sites, Antibody
  • Binding, Competitive / immunology
  • Female
  • Gangliosides / blood
  • Gangliosides / chemistry
  • Gangliosides / immunology*
  • Guillain-Barre Syndrome / complications*
  • Guillain-Barre Syndrome / immunology*
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Immunoglobulin G / physiology
  • Male
  • Middle Aged
  • Protein Conformation

Substances

  • Autoantibodies
  • Gangliosides
  • Immunoglobulin G
  • ganglioside, GD1b