Lambert-Eaton syndrome antibodies target multiple subunits of voltage-gated Ca2+ channels

ABSTRACT 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 α1A, α1B, α1C, and α1E; β3; and α2δ 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 α1 or β3 subunits alone or combined with α2δ subunits, but not α2δ 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 α1 subunits as well as the β3 subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS. Muscle Nerve 51: 176–184, 2015