Neuropediatrics 2006; 37 - MP54
DOI: 10.1055/s-2006-943651

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

X Shu 1, F Cai 1, X Zhang 1
  • 1Children's Hospital, Chongqing University of Medical Science, Chongqing, P.R. China

Objectives: To clarify whether the ganglioside-like structures in C. jejuni lipooligosaccharides (LOS) are crucial for induction of anti-ganglioside antibody responses and neuropathy.

Methods: C. jejuni HB9313 (HS:19) and its galE gene (involved in the biosynthesis of the LOS outer-core oligosaccharide structures) mutant derivative were a gift from Benjamin Fry (Royal Melbourne Institute of Technology University). LOS structures from both strains were analyzed by tricine SDS-PAGE and Western blotting, Cholera toxin B (CTB) subunit binding assay was performed to detect GM1-like structure. 26 guinea pigs were randomly divided into three groups. Group 1 (n=10) was immunized with C. jejuni HS:19 whole-Cell Antigen and adjuvant three times within 3 week, the same procedure were performed in group 2 (n=10) with galE mutant strain and the control group (n=6) with PBS. Serum anti-GM1 antibody was detected by ELISA. Five weeks after the first immunization, all the animals were killed and sciatic nerves were taken for semithin sections, teased fibers and electron microscope examination.

Results: (1) Parental C. jejuni HS:19 expressed LOS of around 5.5 kDa that specifically bound cholera toxin, galE mutant strain expressed a LOS molecule of 4.5 kDa that failed to bind cholera toxin. (2) In group 1, animals developed an enhanced anti-GM1 IgG response by day 14 postimmunization (mean OD: 0.661±0.290) and by day 28 (mean OD: 0.984±0.025), which was statistical significant compared with the control. Howere, no anti-GM1 IgG responses were observed in group 2 or control group. (3) Morphological changes of the sciatic nerves from group 2 were significantly lower than those of group 1 (P<0.05), no statistical difference was found between group 2 and the control.

Conclusion: These findings clarify furtherly that carbohydrate mimicry in C. jejuni LOS is critical for the induction of anti-ganglioside antibody responses and neuropathy.