CARBOHYDRATE MIMICRY OF CAMPYLOBACTER JEJUNI LIPOOLIGOSACCHARIDE IS CRITICAL FOR THE INDUCTION OF ANTI-GM1 ANTIBODY AND NEUROPATHY

Abstract

The expression of ganglioside-mimicking structures of Campylobacter jejuni lipooligosaccharides (LOS) is considered essential for the induction of antiganglioside antibodies that lead to Guillain-Barre syndrome (GBS). The galE gene in C. jejuni is involved in the biosynthesis of the LOS outer-core oligosaccharide structures. We have demonstrated that the C. jejuni HB9313 (HS:19) parental strain expresses a LOS structure containing GM1-like epitopes, and the C. jejuni knockout mutant of the galE gene expresses a truncated LOS structure without GM1-like epitopes. To clarify whether the ganglioside-like structures in Campylobacteri LOS are crucial for induction of antiganglioside antibody responses and neuropathy, we performed immunization experiments in guinea pig models using the parental strain HB9313 and its galE mutant derivative. The anti-GM1 IgG antibody responses in immunized animals were measured by enzyme-linked immunosorbent assay. Sciatic nerve specimens were evaluated pathologically. High levels of the anti-GM1 IgG antibody were induced in guinea pigs immunized with HB9313, but not in those immunized with the galE mutant. The mean percentage of abnormality of sciatic-nerve teased fibers from animals sensitized with C. jejuni HB9313 was significantly higher than from animals immunized with the galE mutant. Furthermore, significant changes were found in semithin sections of the sciatic nerve from animals inoculated with C. jejuni HB9313. The major pathological finding was axonal degeneration; no significant morphological findings, except for occasional demyelination, were observed in animals immunized with the galE mutant. These results indicate that ganglioside-mimicry structures in C. jejuni LOS are necessary for induction of antiganglioside antibody response and neuropathy.