Ganglioside mimicry as a cause of Guillain-Barré syndrome.
OBJECTIVE
Campylobacter jejuni is the most frequent agent of antecedent infection in an axonal variant of Guillain-Barré syndrome, acute motor axonal neuropathy, and anti-GM1 or anti-GD1a IgG antibody is also associated with acute motor axonal neuropathy. Molecular mimicry has been found between human GM1 ganglioside and the lipo-oligosaccharide of C. jejuni isolated from an acute motor axonal neuropathy patient. Progress has been made in Guillain-Barré syndrome research, especially on acute motor axonal neuropathy subsequent to C. jejuni enteritis.


RESULTS
Sensitization of rabbits with C. jejuni lipo-oligosaccharide, as well as GM1, induced the production of anti-GM1 IgG antibody, and the subsequent development of acute flaccid paralysis. Pathological changes in rabbit peripheral nerves were identical to those seen in human acute motor axonal neuropathy. These findings provide conclusive evidence that molecular mimicry is a cause of human autoimmune disease. Ganglioside-like lipo-oligosaccharide is synthesized by sialyltransferase Cst-II, N-acetylgalactosaminyl-transferase CgtA, and galactosyltransferase CgtB. There is a strong association between the simultaneous presence of these genes and Guillain-Barré syndrome-associated C. jejuni strains. Knockout mutants of C. jejuni genes involved in lipo-oligosaccharide sialylation had reduced reactivity with anti-GM1 sera from Guillain-Barré syndrome patients, and did not induce an anti-GD1a IgG antibody response in mice. Lipo-oligosaccharide biosynthesis genes appear to be essential for the induction of anti-GM1 or anti-GD1a IgG antibody and the subsequent development of acute motor axonal neuropathy.


CONCLUSIONS
The concept that carbohydrate mimicry causes autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.
Yuki
Nobuhiro
N
Department of Neurology, Dokkyo University School of Medicine, Tochigi, Japan. yuki@dokkyomed.ac.jp
Odaka
Masaaki
M
D000818:Animals; D001323:Autoantibodies; D002169:Campylobacter Infections / Q000150:complications* / Q000382:microbiology; D016123:Campylobacter jejuni / Q000472:pathogenicity; D005677:G(M1) Ganglioside / Q000009:adverse effects* / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000209:etiology* / Q000382:microbiology; D006801:Humans
D001323:Autoantibodies; D005677:G(M1) Ganglioside