The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré 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.
|Keywords||*Lipopolysaccharides/biosynthesis/chemistry, *Molecular Mimicry, Animals, Autoantibodies/*biosynthesis, Biological Markers, Campylobacter jejuni/chemistry/*genetics, Carbohydrate Conformation, Cross Reactions, Gangliosides/chemistry/*immunology, Genes, Bacterial, Guillain-Barre Syndrome/*immunology, Humans, Mice, Molecular Sequence Data, Mutation, N-Acetylneuraminic Acid/chemistry/immunology, Research Support, Non-U.S. Gov't|
|Journal||Journal of Clinical Investigation|
Jacobs, B.C, Endtz, H.P, Heikema, A.P, Gilbert, M, Komagamine, T, Ang, C.W, … Godschalk, P.C.R. (2004). The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome. Journal of Clinical Investigation. Retrieved from http://hdl.handle.net/1765/8419