Ganglioside mimicry of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity in rabbits

Abstract

The core oligosaccharides of Campylobacter jejuni lipopolysaccharides (LPS) display molecular mimicry with gangliosides. Cross-reactive anti-LPS-antiganglioside antibodies have been implicated to show a crucial role in the pathogenesis of the Guillain-Barré and Miller Fisher syndrome. The specificity of the antiganglioside response is thought to depend on the oligosaccharide structure of the ganglioside mimic. To test this hypothesis and to investigate the potential of LPS from Campylobacter strains from enteritis patients to induce an antiganglioside response, we immunized rabbits with purified LPS from eight Campylobacter jejuni reference strains with biochemically well-defined distinct ganglioside mimics and determined the presence of antiganglioside antibodies. All rabbits produced immunoglobulin G (IgM) and IgG anti-LPS antibodies, and the specificity of the cross-reactive antiganglioside response indeed corresponded with the biochemically defined mimic. Most rabbits also had antibody reactivity against additional gangliosides, and there were slight differences in the fine specificity of the antibody response between rabbits that had been immunized with LPS from the same Campylobacter strain. High anti-LPS and antiganglioside titers persisted over a 10-month period. In conclusion, the structure of the LPS only partly determines the antiganglioside specificity. Other strain-specific as well as host-related factors influence the induction and fine-specificity of the cross-reactive anti-LPS-antiganglioside response.

FIG. 1.

Structures of various C. jejuni LPS used for immunization of rabbits and corresponding ganglioside mimics. Symbols: , N-acetylgalactosamine; □, galactose; ▾, sialic acid; ○, glucose; ⋄, (phosphoryl)ethanolamine; , N-acetylglucosamine; ▪, heptose; ┘, 2-keto-3-deoxy octulosonic acid (KDO); •, dideoxyglucose; ♦, 2-aminoethyl phosphate.