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Immunopathology of the Lambert-Eaton myasthenic syndrome

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Summary

LEMS is an antibody-mediated autoimmune disease that can occur in isolation, or as a paraneoplastic disorder in association with SCLC (60% of patients). The underlying defect is a reduction in the quantal release of the neurotransmitter ACh from the presynaptic nerve terminal at the neuromuscular junction. Experimental evidence indicates the autoantibodies are directed against nerve terminal VGCCs causing downregulation in the number of functional channels by cross-linkage. Functional VGCCs have been detected in SCLC cell lines. In cancer-associated LEMS it appears likely that antibodies initially provoked by tumour VGCCs cross-react with VGCCs at the nerve terminal, causing the clinical disorder.

Antibodies against L-, N- and P-/Q- subtypes of the calcium channels have been identified and radioimmunoassays have been developed to help diagnose the disease. Using peptide toxin 125I-ω-CmTx MVIIC to label P-/Q-type VGCC solubilised from human cerebellum, positive antibody titres can be detected in 85% of patients. However, autoantibodies in LEMS are heterogenous; the antigenic targets include different VGCC subtypes, the intracellular beta subunit and the synaptic vesicle protein synaptotagmin. The disease phenotype may reflect the diversity and titre of these different antibodies.

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  1. Neurosciences Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU, Oxford, UK

    Bethan Lang & John Newsom-Davis

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Lang, B., Newsom-Davis, J. Immunopathology of the Lambert-Eaton myasthenic syndrome. Springer Semin Immunopathol 17, 3–15 (1995). https://doi.org/10.1007/BF00194096

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