Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal

Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence o f high titres of anti-GQ1b ganglioside antibodies, In an ex vivo model, hum an and mouse anti-GQ1b antibodies have been shown previously to induce a co mplement-dependent alpha -latrotoxin-like effect on the murine motor endpla te, i.e. they bring about massive quantal release of acetylcholine and even tually block neuromuscular transmission, Using immunofluorescence microscop y with image analysis, we show here that the late stages of this electrophy siological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III beta -tubulin immunostaining and structural breakdow n of the nerve terminal, as demonstrated by electron microscopy. Ultrastruc turally, axon terminals were disorganized, depleted of vesicles, and subdiv ided 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 .