Ganglioside Mimicry ofCampylobacter jejuniLipopolysaccharides 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 hostrelated factors influence the induction and fine-specificity of the cross-reactive anti-LPS-antiganglioside response.

Isolated insular infarction eliminates contralateral cold, cold pain, and pinprick perception

“…41 The specificity of antiganglioside antibody induced by immunization of C jejuni LOS overall corresponds to ganglioside epitopes on the LOS in rabbits. 42 In this study, we showed that the target ganglioside (GM1, GD1a, or GQ1b) for serum autoantibody corresponds to the LOS-mimicking gangliosides of isolates from individual patients. However, other gangliosides such as GM1b and GalNAc-GD1a could be target antigens for autoantibodies in GBS 30 and further investigation is necessary to explain the variety of the clinical manifestation of GBS in more detail.…”

Mechanisms underlying celiac disease and its neurologic manifestations

“…These bacteria bear lipopolysaccharide (LPS) molecules that cross-react with gangliosides [73][74][75]. In these cases, the antibody specificities have been shown to correspond to the structure of the cross-reactive LPS oligosaccharides [76,77], and production of anti-ganglioside antibodies with the same specificities has been induced by immunization of animals with the LPS species [78]. In CD, a mouse monoclonal immunoglobulin (Ig) G antigliadin antibody has been shown to cross-react with human cerebellar tissue, possibly indicating its involvement in CD ataxia, although the target antigen has not yet been characterized [52].…”

Campylobacter jejuniStrain CG8421: A Refined Model for the Study of Campylobacteriosis and Evaluation ofCampylobacterVaccines in Human Subjects

“…First, a high dose ( colony-forming 9 1 ϫ 10 units [CFUs]) of C. jejuni has been required to achieve a у75% attack rate [10]. Second, the outer lipooligosaccharide (LOS) core of the 81-176 strain synthesizes ganglioside mimics, a mechanism by which C. jejuni infection is thought to induce GBS [11][12][13][14].…”