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 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.
Godschalk
Peggy C R
PC
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. p.godschalk@erasmusmc.nl
Heikema
Astrid P
AP
Gilbert
Michel
M
Komagamine
Tomoko
T
Ang
C Wim
CW
Glerum
Jobine
J
Brochu
Denis
D
Li
Jianjun
J
Yuki
Nobuhiro
N
Jacobs
Bart C
BC
van Belkum
Alex
A
Endtz
Hubert P
HP
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
D001323:Autoantibodies; D015415:Biomarkers; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D019158:N-Acetylneuraminic Acid