Autor(es): Jacobs Bart C,Bullens Roland W M,O'Hanlon Graham M,Ang C Wim,Willison Hugh J,Plomp Jaap J

Resumo: 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 alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-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 alpha-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.

Palavras-Chave: Alpha-latrotoxin; GQ1b; Guillain-Barre´syndrome; Miller Fishersyndrome; Neuromuscular junction

Imprenta: Muscle & Nerve, v. 25, n. 4, p. 549-558, 2002

Identificador do objeto digital: 10.1002/mus.10060

Descritores: Guillain-Barre Syndrome - Biochemistry ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Transmission ; Guillain-Barre Syndrome - Immunology ; Guillain-Barre Syndrome - Public health

Data de publicação: 2002

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