title: The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome.
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.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. p.godschalk@erasmusmc.nl
authors.forename: Peggy C R
authors.initials: PC
authors.lastname: Godschalk
authors.forename: Astrid P
authors.initials: AP
authors.lastname: Heikema
authors.forename: Michel
authors.initials: M
authors.lastname: Gilbert
authors.forename: Tomoko
authors.initials: T
authors.lastname: Komagamine
authors.forename: C Wim
authors.initials: CW
authors.lastname: Ang
authors.forename: Jobine
authors.initials: J
authors.lastname: Glerum
authors.forename: Denis
authors.initials: D
authors.lastname: Brochu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Endtz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015415:Biomarkers; D016123:Campylobacter jejuni / Q000737:chemistry / Q000235:genetics*; D002236:Carbohydrate Conformation; D003429:Cross Reactions; D005732:Gangliosides / Q000737:chemistry / Q000276:immunology*; D005798:Genes, Bacterial; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000737:chemistry; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D019158:N-Acetylneuraminic Acid