Lambert-eaton syndrome antibodies target multiple subunits of voltage-gated Ca2+ 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 α_1A, B, C and E, β_3, and α₂δ of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, a 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 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. Conclusion: 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 2014