Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel autoantibody assays in Lambert-Eaton myasthenic syndrome.

Abstract	Lambert-Eaton myasthenic syndrome (LEMS) is a neurological autoimmune disease in which downregulation of voltage-gated calcium channels (VGCCs) leads to reduced acetylcholine release from motoneuron terminals. 70% of cases are paraneoplastic and rapid diagnosis of LEMS can result in early detection of the underlying tumor. Serological assays based on the capacity of autoantibodies to precipitate VGCCs labeled with radioligands provide valuable data. We have established a novel assay using the spider venom peptide 125I-omega-Phonetoxin IIA (125I-omegaPtxIIA). 125I-omegaPtxIIA labeled recombinant Cav2.1 and Cav2.2 channels and endogenous VGCCs in rat brain membranes. Autoantibodies that immunoprecipitate a 125I-omegaPtxIIA/channel complex were detected in 26/31 (84%) LEMS patients. The patients that were seropositive in the 125I-omegaPtxIIA assay corresponded precisely to the population that was positive for Cav2.1 and/or Cav2.2 antibodies detected using two different omega-conotoxins. Thus, the 125I-omegaPtxIIA assay detects a broader spectrum of autoantibody specificities than current omega-conotoxin-based assays.
Authors	Nicole Martin-Moutot, Luc de Haro, Raquel Gouvea Dos Santos, Yasuo Mori, Michael Seagar
Journal	Neurobiology of disease (Neurobiol Dis) Vol. 22 Issue 1 Pg. 57-63 (Apr 2006) ISSN: 0969-9961 [Print] United States
PMID	16289869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Autoantibodies Cacna1b protein, mouse Calcium Channels Calcium Channels, N-Type Iodine Radioisotopes Neurotoxins Recombinant Fusion Proteins Spider Venoms omega-Conotoxins voltage-dependent calcium channel (P-Q type)
Topics	Adult Aged Animals Autoantibodies (analysis, blood) Binding, Competitive (immunology) Calcium Channels (immunology) Calcium Channels, N-Type (immunology) Early Diagnosis Female Humans Iodine Radioisotopes Lambert-Eaton Myasthenic Syndrome (diagnosis, immunology, physiopathology) Male Middle Aged Neoplasms (complications, immunology) Neurotoxins Radioimmunoassay (methods) Rats Recombinant Fusion Proteins (immunology) Spider Venoms Subcellular Fractions (immunology) Synaptic Membranes (immunology) omega-Conotoxins

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