Autoimmunity to voltage-gated calcium channels

Several review articles on voltage-gated calcium channels (VGCCs) classify VGCCs into five electrophysiological types and 10 genotypes. Each VGCC is distributed in different organs and specialized cells, and various organ-specific human genetic diseases have been reported. Most of the human diseases caused by abnormalities in the VGCCs are genetic diseases. To the best of our knowledge, Lambert-Eaton myasthenic syndrome (LEMS) appears to be the only autoimmune disease for VGCCs. Approximately 90% of LEMS patients are positive for autoantibodies against P/Q-VGCCs in the active zone of nerve endings. On the other hand, about 50% of LEMS patients a tumor-associated neurological syndrome with small cell lung cancer. Neurological symptoms in LEMS patients include weakness of proximal limb muscles, reduced tendon reflexes, autonomic neuropathy, and in 9%-14% of patients, cerebellar ataxia, and paraneoplastic cerebellar degeneration. In the second half of this manuscript, we provide a clinical review with reference to the recently published Practical Guideline for Myasthenia gravis and LEMS 2022 in Japan.