The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome

J Clin Invest. 2004 Dec;114(11):1659-65. doi: 10.1172/JCI15707.

Abstract

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • Biomarkers
  • Campylobacter jejuni / chemistry
  • Campylobacter jejuni / genetics*
  • Carbohydrate Conformation
  • Cross Reactions
  • Gangliosides / chemistry
  • Gangliosides / immunology*
  • Genes, Bacterial
  • Guillain-Barre Syndrome / immunology*
  • Humans
  • Lipopolysaccharides* / biosynthesis
  • Lipopolysaccharides* / chemistry
  • Mice
  • Molecular Mimicry*
  • Molecular Sequence Data
  • Mutation
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Gangliosides
  • Lipopolysaccharides
  • lipid-linked oligosaccharides
  • N-Acetylneuraminic Acid