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

Monospecific high-affinity and complement activating anti-GM1 antibodies are determinants in experimental axonal neuropathy

“…We did not find a significant difference in the antibody titers to GM1 between group I rabbits and group II rabbits confirming that antiganglioside antibodies, even though at high titer, are "per se" not sufficient to cause the experimental neuropathy [14,18]. Rabbits which developed the neuropathy showed higher titers of monospecific and high-affinity anti-GM1 antibodies which were detectable even four weeks before the onset of the neuropathy.…”

“…High-affinity antibodies were also demonstrated in a previous study in rabbits immunized with GM1 and KLH which developed the neuropathy, but these antibodies were not searched in the unaffected rabbits immunized with the same procedure [20]. More recently it was reported that rabbits, immunized with GM1 and KLH, which developed an axonal neuropathy had highaffinity antibodies, whereas the only rabbit immunized with the same procedure, which did not developed the neuropathy did not have highaffinity antibodies [18]. In support of the importance of monospecific antibodies Lardone and co-workers found significant associations between fine specificity and disease severity also in GBS patients [21].…”

“…In different experimental studies all rabbits that developed ataxic or axonal neuropathy and monospecific high-affinity antibodies were immunized with KLH as adjuvant [18][19][20]. KLH is a glycoprotein widely used as a carrier for small molecules to enhance immune responses.…”

“…In ours' and other Authors' experience it has been difficult to replicate consistently the axonal experimental model [15][16][17][18]. Recently the presence of monospecific and high-affinity anti-ganglioside antibodies has been associated with the induction of experimental ataxic and axonal neuropathy in rabbits and with disease severity in human GBS [18][19][20][21].…”

“…Recently the presence of monospecific and high-affinity anti-ganglioside antibodies has been associated with the induction of experimental ataxic and axonal neuropathy in rabbits and with disease severity in human GBS [18][19][20][21]. Human GBS is associated with IgG1 and IgG3 isotypes, which need CD40l involvement.…”