Structure of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity and clinical features of Guillain-Barré and Miller Fisher patients

Abstract

Ganglioside mimicry in the lipopolysaccharide (LPS) fraction of Campylobacter jejuni isolated from Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) patients was compared with isolates from patients with an uncomplicated enteritis. The antibody response to C. jejuni LPS and gangliosides in neuropathy patients and controls was compared as well. LPS from GBS and MFS-associated isolates more frequently contained ganglioside-like epitopes compared to control isolates. Almost all neuropathy patients showed a strong antibody response against LPS and multiple gangliosides in contrast to enteritis patients. Isolates from GBS patients more frequently had a GM1-like epitope than isolates from MFS patients. GQ1b-like epitopes were present in all MFS-associated isolates and was associated with anti-GQ1b antibody reactivity and the presence of oculomotor symptoms. These results demonstrate that the expression of ganglioside mimics is a risk factor for the development of post-Campylobacter neuropathy. This study provides additional evidence for the hypothesis that the LPS fraction determines the antiganglioside specificity and clinical features in post-Campylobacter neuropathy patients.

FIG. 1.

Structure of C. jejuni LPS types and the corresponding ganglioside mimics. Symbols: ○, N-acetylgalactosamine; □, galactose; ○, glucose; ▾, sialic acid; ◊, (phosphoryl)ethanolamine; , N-acetylglucosamine; ▪, heptose; ▨, 3-deoxy-d-manno-octulosonic acid; •, dideoxyglucose; ⧫, 2-aminoethyl phosphate.

FIG. 2.

C. jejuni LPS reacts differentially with antiganglioside antisera. Purified LPSs were tested for reactivity against a panel of serum samples containing antiganglioside reactivity against GM1 and GA1 (GM1), GQ1b and GD3 (GQ1b), or other gangliosides and/or a combination of GA1 and GQ1b (“other”). (A and B) LPS from GBS patients GB11 and GB16 reacted with sera of the GM1 group. In panel B, LPS from GBS patient GB16, who has an overlap of GBS and MFS, reacted with the sera of the GM1, GQ1b, and “other” groups. (C) LPS from MFS patient MF8 reacted predominantly with GQ1b sera. (D) LPS from the O:19 serostrain reacted with sera of the GM1 group but not with those of the GQ1b group, whereas LPS from the O:10 serostrain reacted with the sera from the GQ1b group. (F) LPS from the O:3 serostrain, which does not contain a GM1- or GQ1b-like structure, did not react with any of the sera. None of the LPS fractions reacted with sera from the healthy controls (HC). Dashed lines indicate the cutoff values.

FIG. 3.

Differential binding of CT and MAb Ha1rbc to C. jejuni LPS from patients with GBS, MFS, and uncomplicated enteritis (Ent). Purified C. jejuni LPS was coated onto 96-well plates and incubated with CT (biotin labeled) (A) or Ha1rbc (B). The differences in binding were compared between GBS and MFS isolates and between neuropathy-associated and uncomplicated enteritis isolates.