Diseases of the myoneural junction.
LEMS appears to associate specifically with SCLC but not with other lung tumors. Experimental and clinical evidence indicates that the autoantibody response is triggered by tumor VGCC determinants, cross-reactivity with determinants at motor nerve terminals leading to the neurological disorder. LEMS currently provides the only example of a paraneoplastic autoantibody-mediated neurological disorder that meets the critical criterion of passive transfer to experimental animals by systemic IgG injections. In young-onset MG cases, the rate of anti-AChR antibody synthesis by cultured thymic cells correlates strongly with the serum titer, and the spectrum of fine specificities are closely matched. Thymic myoid cells contain AChRs, which may in part account for the special role of the thymus in this disease. Recombinant human AChR alpha-subunit has proved more efficient than Torpedo AChR in stimulating T-cell responses in myasthenic peripheral blood and in raising T-cell lines, attributable to the lack of complete homology of Torpedo AChR with the human receptor. The use of recombinant AChR fragments to test responsiveness in T-cell lines and clones raised against the full-length alpha-subunit should enable the regions containing the critical T-cell epitopes to be further defined and the ability of these clones to provide helper activity in specific antibody production to be tested.
Department of Clinical Neurology, Radcliffe Infirmary, University of Oxford, England.
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Newsom-Davis
D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D006801:Humans; D007473:Ion Channels / Q000276:immunology; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology; D009468:Neuromuscular Diseases / Q000276:immunology*; D009469:Neuromuscular Junction / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D001323:Autoantibodies; D007473:Ion Channels; D011950:Receptors, Cholinergic