title: Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis.
abstract: METHODS
  Sporadic amyotrophic lateral sclerosis is a chronic, progressive degenerative disease of the motor neurons of the spinal cord and motor cortex. The cause is unknown. Recent electrophysiologic studies in animals indicate that immunoglobulins from patients with this disease alter presynaptic voltage-dependent calcium currents and calcium-dependent release of neurotransmitters. To determine whether similar interactions might be identified biochemically, we used an enzyme-linked immunosorbent assay (ELISA) to detect the reaction of serum IgG with purified complexes of L-type voltage-gated calcium channels from rabbit skeletal muscle. The results from patients with amyotrophic lateral sclerosis were compared with those obtained from patients with other types of motor neuron disease, patients with autoimmune and non-autoimmune neurologic diseases, and normal subjects.
  
  
  RESULTS
  Serum samples from 36 of 48 patients with sporadic amyotrophic lateral sclerosis (75 percent) contained IgG that reacted with L-type calcium-channel protein, and serum reactivity on ELISA correlated with the rate of disease progression (Spearman rank-correlation coefficient, 0.62). Reactive serum was present in only 1 of 25 normal subjects and 1 of 35 control patients with no motor neuron disease. Antibodies to L-type voltage-gated calcium channels were identified in 6 of 9 patients with Lambert-Eaton syndrome, and in 3 of 15 patients with Guillain-Barré syndrome.
  
  
  CONCLUSIONS
  Antibodies to L-type voltage-gated calcium channels are present in the serum of patients with amyotrophic lateral sclerosis, and antibody titers correlate with the rate of disease progression. Together with previous data, these results suggest a role for autoimmune mechanisms in the pathogenesis of sporadic amyotrophic lateral sclerosis.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Hamilton
authors.forename: F
authors.initials: F
authors.lastname: Hofmann
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.forename: W
authors.initials: W
authors.lastname: Nastainczyk
authors.forename: L
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: E
authors.initials: E
authors.lastname: Stefani
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D015220:Calcium Channels / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000276:immunology; D011817:Rabbits
chemical_list: D001323:Autoantibodies; D015220:Calcium Channels; D007074:Immunoglobulin G