Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum

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Abstract
Recent studies suggested that autoantibodies that bind to voltage‐dependent calcium channels and activate calcium entry may play a role in the progressive degeneration of motoneurons in sporadic amyotrophic lateral sclerosis. Immunoassays were performed to assess autoantibody titer in patients with amyotrophic lateral sclerosis or Lambert‐Eaton myasthenic syndrome, a disease in which the presnce of anti‐calcium channel antibodies is well documented. Based on immunoprecipitation assays for antibodies against N‐type calcium channels, only 8% (2/25) of amyotrophic lateral sclerosis patients had marginally positive titers, whereas 58% (18/31) of patients with Lambert‐Eaton myasthenic syndrome had positive titers. Enzyme‐linked immunosorbent assays with purified neuronal N‐type calcium channels revealed immunoreactivity in 2 of 25 amyotrophic lateral sclerosis sera and 12 of 31 Lambert‐Eaton myasthenic syndrome sera, which is not compatible with suggestions that enzyme‐linked immunosorbent assay is a more sensitive technique for the detection of autoantibodies in amyotrophic lateral sclerosis. Furthermore, based on immunoprecipitation assays, amyotrophic lateral sclerosis sera were totally negative for antibodies against L‐type calcium channels from skeletal muscle or brain. These data do not support the hypothesis that an autoimmune response against calcium channels plays a primary role in amyotrophic lateral sclerosis.