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

Abstract

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with
\\n gangliosides in nervous tissue is considered to induce cross-reactive
\\n antibodies that lead to Guillain-Barre syndrome (GBS), an acute
\\n polyneuropathy. To determine whether specific bacterial genes are crucial
\\n for the biosynthesis of ganglioside-like structures and the induction of
\\n anti-ganglioside antibodies, we characterized the C. jejuni LOS
\\n biosynthesis gene locus in GBS-associated and control strains. We
\\n demonstrated that specific types of the LOS biosynthesis gene locus are
\\n associated with GBS and with the expression of ganglioside-mimicking
\\n structures. Campylobacter knockout mutants of 2 potential GBS marker
\\n genes, both involved in LOS sialylation, expressed truncated LOS
\\n structures without sialic acid, showed reduced reactivity with GBS patient
\\n serum, and failed to induce an anti-ganglioside antibody response in mice.
\\n We demonstrate, for the first time, to our knowledge, that specific
\\n bacterial genes are crucial for the induction of anti-ganglioside
\\n antibodies.