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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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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
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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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creator	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
description	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.
doi_str_mv	10.1172/JCI200415707
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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. 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We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.</description><subject>Acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Autoantibodies - biosynthesis</subject><subject>Biomarkers</subject><subject>Biomedical research</subject><subject>Biosynthesis</subject><subject>Campylobacter</subject><subject>Campylobacter jejuni - chemistry</subject><subject>Campylobacter jejuni - genetics</subject><subject>Carbohydrate Conformation</subject><subject>Cross Reactions</subject><subject>Gangliosides - chemistry</subject><subject>Gangliosides - immunology</subject><subject>Genes</subject><subject>Genes, Bacterial</subject><subject>Guillain-Barre syndrome</subject><subject>Guillain-Barre Syndrome - immunology</subject><subject>Humans</subject><subject>Lipopolysaccharides - biosynthesis</subject><subject>Lipopolysaccharides - chemistry</subject><subject>Mice</subject><subject>Molecular Mimicry</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>N-Acetylneuraminic Acid - 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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
title	The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome
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