Complex of GM1- and GD1a-like lipo-oligosaccharide mimics GM1b, inducing anti-GM1b antibodies.

Abstract

OBJECTIVE:

Molecular mimicry between Campylobacter jejuni lipo-oligosaccharides (LOSs) and human gangliosides GM1 and GD1a induces the production of anti-GM1 and anti-GD1a antibodies, and the development of Guillain-Barré syndrome. Complexes of two different gangliosides form new molecular shapes capable of enhancing recognition by anti-ganglioside antibodies. To test the hypothesis that the complex of GM1-like and GD1a-like LOSs of C. jejuni induces the development of anti-GM1b antibodies in Guillain-Barré syndrome patients.

METHODS:

Mass spectrometry analysis determined the LOS outer core structures, with which mice were immunized. IgG antibodies to single gangliosides and complex of gangliosides were tested in sera from Guillain-Barré syndrome patients from whom C. jejuni LOS had been isolated.

RESULTS:

Two isolates from GBS patients who had anti-GM1b antibodies, but neither anti-GM1 nor -GD1a antibodies, expressed both GM1-like and GD1a-like LOSs, but not GM1b-like LOS. Anti-GM1b antibodies were induced in one of the mice immunized with the C. jejuni bearing GM1-like and GD1a-like LOS. Sera from 20 patients had antibodies to the complex of GM1 and GD1a, all of which carried anti-GM1b reactivity. Five of these sera harbored neither anti-GM1 nor anti-GD1a antibodies. IgG antibodies to the complex were absorbed by GM1b, but by neither GM1 nor GD1a.

CONCLUSIONS:

GM1-like and GD1a-like LOSs form a GM1b epitope, inducing the development of anti-GM1b antibodies in patients with Guillain-Barré syndrome subsequent to C. jejuni enteritis. Here, we present a new paradigm that the complex of two different structures forms a new molecular mimicry, inducing the production of autoantibodies.

• Authors: Michiaki Koga, Michel Gilbert, Jianjun Li, Nobuhiro Yuki
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0124004 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25867522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gangliosides
• Lipopolysaccharides
• lipid-linked oligosaccharides
• ganglioside, GD1a
• G(M1) Ganglioside
• ganglioside M1b

Topics

• Animals
• Antibody Formation
• Campylobacter jejuni (chemistry)
• Cross Reactions
• Enzyme-Linked Immunosorbent Assay
• G(M1) Ganglioside (analogs & derivatives, chemistry, immunology)
• Gangliosides (chemistry)
• Humans
• Lipopolysaccharides (chemistry)
• Mice
• Molecular Mimicry