Neuropathophysiological potential of Guillain-Barré syndrome anti-ganglioside-complex antibodies at mouse motor nerve terminals

Zitman, F.M.P. et al. (2011) Neuropathophysiological potential of Guillain-Barré syndrome anti-ganglioside-complex antibodies at mouse motor nerve terminals. Clinical and Experimental Neuroimmunology, 2(3), pp. 59-67. (doi:10.1111/j.1759-1961.2011.00022.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1759-1961.2011.00022.x

Abstract

Objectives:  Anti-ganglioside antibodies are present in approximately half of Guillain–Barré syndrome (GBS) patients. Recently, it has been shown that a considerable proportion of these patients has serum antibodies against antigenic epitopes formed by a complex of two different gangliosides. However, direct experimental evidence for neuropathogenicity of this special category of antibodies is currently lacking. Here, we explored a series of GBS and GBS-variant sera with anti-ganglioside-complex antibodies for their ability to induce complement-dependent deleterious effects at the living neuronal membrane. Methods:  The neuropathophysiological potential of 31 GBS sera containing either anti-GM1/GD1a- or anti-GM1/GQ1b-ganglioside-complex antibodies was studied at motor nerve terminal presynaptic membranes in the mouse phrenic nerve/diaphragm muscle ex vivo experimental model. With electrophysiological measurements and confocal fluorescence microscopy, we assessed and quantified the damaging effect on neuronal membranes by anti-ganglioside-complex antibodies. Results:  We show that anti-GM1/GD1a- and anti-GM1/GQ1b-ganglioside-complex positive sera can induce complement-mediated functional and morphological injury at mouse motor nerve terminals ex vivo. Of the 31 investigated anti-ganglioside-complex patient sera, 17 sera induced increases in miniature end-plate potential frequency in this experimental model, mostly associated with muscle fibre twitches. Variability in potency was observed, with the anti-GM1/GD1a-complex sera inducing the most outspoken effects. Conclusions:  The present study shows the presence of ganglioside-complexes as available antigens in living neuronal membranes and supplies proof-of-principle that anti-ganglioside-complex antibodies in sera from GBS patients can induce complement-mediated damage. This strongly supports the hypothesis that autoimmune targeting of ganglioside-complexes is of pathogenic relevance in a proportion of GBS patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willison, Professor Hugh
Authors: Zitman, F.M.P., Greenshields, K.N., Kuijf, M.L., Ueda, M., Kaida, K.I., Broos, L.A.M., Tio-Gillen, A.P., Jacobs, B.C., Kusunoki, S., Willison, H.J., and Plomp, J.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Clinical and Experimental Neuroimmunology
ISSN:1759-1961
Published Online:24 June 2011
Copyright Holders:Copyright © 2011 Wiley Blackwell
First Published:First published in Clinical and Experimental Neuroimmunology 2011, 2(3):59-67
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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