Autoimmunity to voltage‐gated calcium channels

Abstract

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.