Neurológia pre prax 2/2010

Autoantibody-mediated disorders of the neuromuscular junction

The neuromuscular junction is the most accesible synapse in the nervous system and is very susceptible to circulating factors, notably neurotoxins and specific autoantibodies. Research advances have shown that key transmembrane proteins at the neuromuscular junction are vulnerable to antibody-mediated autoimmune attack. Autoantibodies lead to loss of the specific ion channels causing physiological defects in neuromuscular transmission. Main antigenic targets are acetylcholine receptors (AChRs) and muscle specific kinase (MuSK) in myasthenia gravis, voltage-gated calcium channels (VGCCs) in the Lambert-Eaton myasthenic syndrome (LEMS), voltage-gated potassium channels (VGKCs) in neuromyotonia and GQ1b ganglioside in Miller Fisher syndrome (MFS). Autoantibodies can be measured in patients sera by immunoprecipation of detergent-extracted ion channels radioactivelly-labelled with high affinity 125I-neurotoxins. The pathogenetic role of the circulating antibodies can be demonstrated by passive transfer to mice, and by the clinical improvement that follows plasma exchange and other immunotherapies. This paper will briefly discuss the role of circulating autoantibodies in autoimmune disorders of neuromuscular transmission: seropositive myasthenia gravis, myasthenia gravis with MuSK antibodies, seronegative myasthenia, transient neonatal myasthenia, arthrogryposis multiplex congenita, LEMS, acquired neuromytonia and MFS.

Keywords: neuromuscular junction, circulating autoantibodies, antigens (AchRs; MuSK; VGCCs; VGKC; GQ1b ganglioside), imunotherapy, plasmapheresis.