Guillain-Barré Syndrome- and Miller Fisher Syndrome-Associated Campylobacter jejuni Lipopolysaccharides Induce Anti-GM ₁ and Anti-GQ _1b Antibodies in Rabbits

Abstract

Campylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with GuillainBarré syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purified LPS fractions from five Campylobacter strains to induce antiganglioside responses in rabbits. The animals that received injections with LPS from GBS-associated strains developed anti-GM 1 and anti-GA 1 antibodies. Animals injected with LPS from one MFS-related C. jejuni strain produced anti-GQ 1b antibodies. Rabbits that were injected with Penner O:3 LPS had a strong anti-LPS response, but no antiganglioside reactivity was observed. The antiganglioside specificity in the rabbits reflected the specificity in the patients from whom the strains were isolated. In conclusion, our results indicate that an immune response against GBS-and MFS-associated C. jejuni LPS results in antiganglioside antibodies. These results provide strong support for molecular mimicry as a mechanism in the induction of antiganglioside antibodies following infections.

Ganglioside Mimicry ofCampylobacter jejuniLipopolysaccharides Determines Antiganglioside Specificity in Rabbits

“…Our studies confirm and extend earlier reports with LPS from Campylobacter strains isolated from GBS, MFS, and uncomplicated enteritis patients (1,12,28,35).…”

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

“…Chemical and structural analysis of lipopolysaccharide (LPS) and lipooligosaccharide (LOS) outer core oligosaccharide (core OS) structures from C. jejuni serotypes isolated from GBS and non-GBS patients have identified sialylated moieties with configurations identical to those of several gangliosides (9,11,42,44,45,50). For example, LPSs from C. jejuni HS:19, a serotype commonly associated with GBS, have been shown to contain GM1-, GD1a-, GD3-, and GT1a-like motifs, and antibody mimicry is supported by the finding that immunization of experimental animals with these LPSs produces the corresponding anti-ganglioside antibody response (4,18). Serotyping studies have determined that certain C. jejuni serotypes, including HS:19, have greater potential for triggering GBS, and this may be due to quantitative differences in ganglioside-like LPS and LOS epitopes compared with non-GBS-associated strains (9,44,50).…”

Characterization of Two Campylobacter jejuni Strains for Use in Volunteer Experimental-Infection Studies

“…The mimic most often associated with GBS is GM 1 , and the mimic most often associated with the Miller Fisher variant of GBS, which affects the ocular nerves, is GQ 1b (4,9,61). Recently, it was demonstrated that the immunization of rabbits with purified C. jejuni LOS containing a GM 1 mimic resulted in high levels of anti-GM 1 antibodies and symptoms of GBS in the animals (2,64).…”