title: Antibodies to active zone protein ERC1 in Lambert-Eaton myasthenic syndrome.
abstract: Lambert-Eaton myasthenic syndrome (LEMS) is characterized by fluctuating muscle weakness and autonomic dysfunction. In 90% of the LEMS patients the disease is associated with auto-antibodies against the voltage-gated calcium channels (VGCC). Several auto-immune responses against other antigenic targets have been described to (co)-occur in LEMS patients. To identify new LEMS associated small cell lung cancer (SCLC) markers immunoprecipitation with a SCLC cell line was performed. We discovered strong immunoreactivity against the 120 kDa large ERC1 protein in one tumor-negative VGCC-positive LEMS patient. A recombinant ELISA assay and a cellular assay expressing GFP-tagged full length ERC1 were used to confirm the presence of auto-antibodies against ERC1 in this patient. Additional testing of 58 LEMS patients including 9 VGCC auto-antibody negative LEMS patients, 48 myasthenia gravis patients, 84 control patients with other diseases and 12 healthy controls revealed no other cases. ERC1 is therefore a new, but rare, antigen in LEMS.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. M.G.M.Huijbers@lumc.nl
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Huijbers
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Lipka
authors.forename: Marko
authors.initials: M
authors.lastname: Potman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hensbergen
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
authors.forename: Erik H
authors.initials: EH
authors.lastname: Niks
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: Rinse
authors.initials: R
authors.lastname: Klooster
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Verschuuren
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D015220:Calcium Channels / Q000276:immunology; D002460:Cell Line; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000150:complications / Q000276:immunology*; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000276:immunology*; D055752:Small Cell Lung Carcinoma / Q000150:complications / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; D001324:Autoantigens; D015220:Calcium Channels; C468925:ERC1 protein, human; D009419:Nerve Tissue Proteins