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

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 biosynthe...

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Bibliographic Details
Published in:The Journal of clinical investigation 2004-12, Vol.114 (11), p.1659-1665
Main Authors: Godschalk, Peggy C R, Heikema, Astrid P, Gilbert, Michel, Komagamine, Tomoko, Ang, C Wim, Glerum, Jobine, Brochu, Denis, Li, Jianjun, Yuki, Nobuhiro, Jacobs, Bart C, van Belkum, Alex, Endtz, Hubert P
Format: Article
Language:English
Subjects:
Acids
Animals
Antibodies
Autoantibodies - biosynthesis
Biomarkers
Biomedical research
Biosynthesis
Campylobacter
Campylobacter jejuni - chemistry
Campylobacter jejuni - genetics
Carbohydrate Conformation
Cross Reactions
Gangliosides - chemistry
Gangliosides - immunology
Genes
Genes, Bacterial
Guillain-Barre syndrome
Guillain-Barre Syndrome - immunology
Humans
Lipopolysaccharides - biosynthesis
Lipopolysaccharides - chemistry
Mice
Molecular Mimicry
Molecular Sequence Data
Mutation
N-Acetylneuraminic Acid - chemistry
N-Acetylneuraminic Acid - immunology
Serology
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI200415707