Validation of a rabbit model of neuropathy induced by immunization with gangliosides.

The induction of neurological signs by immunization of rabbits with gangliosides has been a controversial topic for many years. Recently, Yuki et al. [N. Yuki, M. Yamada, M. Koga, M. Odaka, K. Susuki, Y. Tagawa, et al. Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganglioside. Ann Neurol 2001;49:712-720.] described an immunization protocol, including keyhole lympet hemocyanin in addition to ganglioside that induced a neurological disease resembling human Guillain-Barré syndrome. We employed this protocol in our laboratory and succeeded in reproducing the disease. Five different experiments were performed during a period of two years by different operators, using different batches of drugs, in a total of 26 rabbits. Despite minor variations in onset time and severity of the induced disease, the model proved to be reproducible. Both gangliosides and keyhole limpet hemocyanin are required for induction of disease.

Unusual presence of anti-GM1 IgG-antibodies in a healthy individual, and their possible involvement in the origin of disease-associated anti-GM1 antibodies.

Anti-GM1 antibodies of the IgG isotype are found in serum from patients with Guillain-Barré syndrome. In normal human sera, anti-GM1 IgM-antibodies are commonly present, but their IgG counterpart has not been previously demonstrated. During routine screening, we found a normal human serum with a high titer of anti-GM1 IgG-antibodies (IgG1 subclass). Affinity estimation by soluble antigen-binding inhibition indicated that they are low-affinity antibodies with IC50 values between one and two orders of magnitude higher than those of anti-GM1 IgG-antibodies from Guillain-Barré patients. Various antibody parameters remained fairly constant for 1 year, in additional serum samples taken at 4-month intervals. Such anti-GM1 IgG1-antibodies were not detected in > 100 other normal serum samples tested, indicating a very low frequency in the general population. The low affinity of these unusually present antibodies could explain the absence of disease, despite their relatively high titer. The significance of this finding in the origin of disease-associated anti-GM1 antibodies is discussed.