Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum.
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 presence 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.
Arsac
C
C
INSERM U374, Institut Jean Roche, Faculté de Médecine Secteur Nord, Marseille, France.
Raymond
C
C
Martin-Moutot
N
N
Dargent
B
B
Couraud
F
F
Pouget
J
J
Seagar
M
M
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000276:immunology* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017275:Isradipine / Q000378:metabolism; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood / Q000276:immunology*; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D012680:Sensitivity and Specificity; D020866:omega-Conotoxin GVIA
D001323:Autoantibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010455:Peptides; D020866:omega-Conotoxin GVIA; D017275:Isradipine