Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of α-latrotoxin (α-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the α-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross- reactivity to related gangliosides) are responsible for the α-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.

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Muscle & Nerve
Department of Neurology

Jacobs, B., Bullens, R., O'Hanlon, S., Ang, W., Willison, H., & Plomp, J. (2002). Detection and prevalence of α-latrotoxin-like effects of serum from patients with Guillain-Barré syndrome. Muscle & Nerve, 25(4), 549–558. doi:10.1002/mus.10060