The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome
January 2004
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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.
- Animals
- Humans
- Research Support, Non-U.S. Gov't
- Mice
- Molecular Sequence Data
- Mutation
- Genes, Bacterial
- Biological Markers
- Cross Reactions
- *Lipopolysaccharides/biosynthesis/chemistry
- *Molecular Mimicry
- Autoantibodies/*biosynthesis
- Gangliosides/chemistry/*immunology
- Guillain-Barre Syndrome/*immunology
- N-Acetylneuraminic Acid/chemistry/immunology
- Carbohydrate Conformation
- Campylobacter jejuni/chemistry/*genetics
- strain
- structure
- jejuni
- class
- antibody
- locus
- campylobacter
- jejuni strains
- mutant
- orf 10/orf mutants
- cst-ii
- biosynthesi
- patient
- orf 11
- ganglioside
- los locus
- figure
- sialic
- sialic acid
- ganglioside mimics
