Lambert-Eaton syndrome antibodies target multiple subunits of voltage-gated Ca super(2+) channels

Introduction: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular disorder. Autoantibodies against subunits of voltage-gated calcium channels (VGCCs) associated with acetylcholine release are thought to cause LEMS. Methods: HEK293 cells expressing specific individual recombinant subunits of alpha sub(1A), alpha sub(1B), alpha sub(1C), and alpha sub(1E); beta sub(3); and alpha sub(2) delta of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, 1 patient with small-cell lung carcinoma, and 1 with myasthenia gravis. Results: All LEMS patient antibodies bound to cells containing any of the alpha sub(1) or beta sub(3) subunits alone or combined with alpha sub(2) delta subunits, but not alpha sub(2) delta alone. Autoantibodies from the patient with small-cell lung carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits. Conclusions: Autoantibodies from LEMS patients bind directly to multiple VGCC alpha sub(1) subunits as well as the beta sub(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS. Muscle Nerve 51: 176-184, 2015