IMMUNOASSAYS FAIL TO DETECT ANTIBODIES AGAINST NEURONAL CALCIUM CHANNELS IN AMYOTROPHIC-LATERAL-SCLEROSIS SERUM

Recent studies suggested that autoantibodies that bind to voltage-depe ndent calcium channels and activate calcium entry may play a role in t he progressive degeneration of motoneurons in sporadic amyotrophic lat eral sclerosis. Immunoassays were performed to assess autoantibody tit er in patients with amyotrophic lateral sclerosis or Lambert-Eaton mya sthenic syndrome, a disease in which the presence of anti-calcium chan nel antibodies is well documented. Based on immunoprecipitation assays for antibodies against N-type calcium channels, only 8% (2/25) of amy otrophic lateral sclerosis patients had marginally positive titers, wh ereas 58% (18/31) of patients with Lambert-Eaton myasthenic syndrome h ad positive titers. Enzyme-linked immunosorbent assays with purified n euronal N-type calcium channels revealed immunoreactivity in 2 of 25 a myotrophic lateral sclerosis sera and 12 of 31 Lambert-Eaton myastheni c syndrome sera, which is not compatible with suggestions that enzyme- linked immunosorbent assay is a more sensitive technique for the detec tion of autoantibodies in amyotrophic lateral sclerosis. Furthermore, based on immunoprecipitation assays, amyotrophic lateral sclerosis ser a were totally negative for antibodies against L-type calcium channels from skeletal muscle or brain. These data do not support the hypothes is that an autoimmune response against calcium channels plays a primar y role in amyotrophic lateral sclerosis.