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

Abstract

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. HEK293 cells expressing specific individual recombinant subunits of α(1A), α(1B), α(1C), and α(1E); β(3); and α(2)δ of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, 1 patient with small-cell lung carcinoma, and 1 with myasthenia gravis. All LEMS patient antibodies bound to cells containing any of the α(1) or β(3) subunits alone or combined with α(2)δ subunits, but not α(2)δ alone. Autoantibodies from the patient with small-cell lung carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits. Autoantibodies from LEMS patients bind directly to multiple VGCC α(1) subunits as well as the β(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS.