Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome
Article first published online: 3 MAY 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 51, Issue 6, pages 673–680, June 2002
How to Cite
Buchwald, B., Ahangari, R., Weishaupt, A. and Toyka, K. V. (2002), Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome. Ann Neurol., 51: 673–680. doi: 10.1002/ana.10205
- Issue published online: 21 MAY 2002
- Article first published online: 3 MAY 2002
- Manuscript Accepted: 11 FEB 2002
- Manuscript Revised: 8 FEB 2002
- Manuscript Received: 16 NOV 2001
- Deutsche Forschungsgemeinschaft. Grant Number: DFG,TO 61/9-2 (K.V.T., B.B.)
Intravenous immunoglobulin (IVIg) treatment ameliorates the course of Guillain-Barré syndrome (GBS), but its specific mode of action is unknown. We attempted to delineate the effect of IVIg on neuromuscular blocking antibodies in GBS. A total of seven GBS serum samples were examined for blocking antibodies and the effect of IVIg with a macro-patch-clamp technique in mouse hemidiaphragms. First, serum was tested before and after treatment with IVIg. Second, we investigated with coincubation experiments whether the IVIg was capable of neutralizing neuromuscular blocking antibodies in GBS serum or affinity-purified immunoglobulin G (IgG) fractions. Finally, the mechanism of the neutralizing effect was studied by the coincubation of active blocking GBS IgG with Fab and Fc fragments prepared from IVIg. All GBS sera (two adults and two children) and GBS IgG fractions (three adults) taken before treatment with IVIg blocked evoked quantal release by approximately 90%. Blocking activity was markedly reduced in sera obtained after treatment with IVIg. Coincubation of the pretreatment blocking serum with the posttreatment serum, or with the IVIg preparation used for treatment, reduced the blocking activity of the pretreatment GBS serum. When GBS IgG was coincubated with IVIg, the blocking activity of GBS IgG was diminished dose-dependently. Monovalent and divalent Fab fragments prepared from the IVIg were as effective as whole IVIg, but Fc fragments were ineffective. Therapeutic IVIg is capable of neutralizing neuromuscular blocking antibodies in GBS by a dose-dependent, antibody-mediated mechanism. This may, in part, explain its therapeutic efficacy.