High affinity of anti‐GM₁ antibodies is associated with disease onset in experimental neuropathy

Abstract

High antibody affinity has been proposed as a disease determinant factor in neuropathies associated with anti-GM1 antibodies. An experimental model of Guillain-Barré syndrome, induced by immunization of rabbits with bovine brain gangliosides or GM1, was described recently (Yuki et al. [2001] Ann. Neurol. 49:712-720). We searched plasma from these rabbits, taken at disease onset and 1 or 2 weeks prior to onset, for the presence of high-affinity anti-GM1 IgG antibodies. Affinity was estimated by soluble antigen binding inhibition. High-affinity antibodies (binding inhibition by 10(-9) M GM1) were detected at disease onset but not before. No such difference was found for other antibody parameters such as titer, fine specificity, and population distribution. These findings support the proposed role of high affinity as an important factor in disease induction by anti-GM1 antibodies.

Anti-GM1 Antibodies Cause Complement-Mediated Disruption of Sodium Channel Clusters in Peripheral Motor Nerve Fibers

“…Anti-GM1 IgG antibody titers do not differ between rab- bits that develop paralysis and that do not manifest clinical findings under the same immunization protocol (van Sorge et al, 2007). Other factors such as the affinity of the antibodies may be involved in disease induction by anti-GM1 antibodies (Comín et al, 2006). Thin-layer chromatography with immunostaining confirmed the reactivity of IgG with GM1 ( Fig.…”

Ganglioside mimicry and peripheral nerve disease

“…87 Plasma from rabbits, taken at disease onset and 1 or 2 weeks prior to onset, were tested for the presence of high-affinity anti-GM1 IgG antibody. 11 Affinity was estimated from soluble antigen-binding inhibition. High-affinity antibodies (binding inhibition by 10 Ϫ9 M GM1) were detected at disease onset but not before.…”

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

“…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].…”

“…Binding inhibition of anti-GM1 monospecific antibodies to solidphase adsorbed GM1 by soluble GM1 was calculated: OD of the wells containing the complex with soluble GM1 and anti-GM1 monospecific antibodies/OD of the wells with anti-GM1 monospecific antibodies (%). Anti-GM1 were judged high-affinity antibodies in the presence of binding inhibition by 10 − 9 M soluble GM1 [20].…”

“…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.…”