title: Lambert-Eaton syndrome antibodies target multiple subunits of voltage-gated Ca2+ channels.
abstract: BACKGROUND
  Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular disorder. Autoantibodies against subunits of voltage-gated calcium channels (VGCCs) associated with acetylcholine release are thought to cause LEMS.
  
  
  METHODS
  HEK293 cells expressing specific individual recombinant subunits of α(1A), α(1B), α(1C), and α(1E); β(3); and α(2)δ of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, 1 patient with small-cell lung carcinoma, and 1 with myasthenia gravis.
  
  
  RESULTS
  All LEMS patient antibodies bound to cells containing any of the α(1) or β(3) subunits alone or combined with α(2)δ subunits, but not α(2)δ alone. Autoantibodies from the patient with small-cell lung carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits.
  
  
  CONCLUSIONS
  Autoantibodies from LEMS patients bind directly to multiple VGCC α(1) subunits as well as the β(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, B331 Life Sciences Building, 1355 Bogue Street, East Lansing, Michigan, 48824-1317, USA.
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Hajela
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Huntoon
authors.forename: William D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D015220:Calcium Channels / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood / Q000276:immunology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D001323:Autoantibodies; D015220:Calcium Channels; D021122:Protein Subunits; D049452:Green Fluorescent Proteins
keywords: Lambert-Eaton myasthenic syndrome; acetylcholine release; neuromuscular disease; small-cell lung carcinoma; voltage-gated Ca2+ channels