Brain, Vol. 124, No. 5, 893-906,
May 2001
© 2001 Oxford University Press
Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal
1 University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, 4 Department of Biological Sciences, Glasgow Caledonian University, 6 Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK, Neurology, Leiden University Medical Centre, The Netherlands and 2 Departments of Physiology and 5 Neurosciences/NC30,Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
Correspondence to:
Dr Hugh J. Willison, University Department of Neurology, Southern General Hospital, Glasgow G51 4TF, UK E-mail: h.j.willison{at}udcf.gla.ac.uk
Miller–Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent 
-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III ß-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.
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