Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel autoantibody assays in Lambert-Eaton myasthenic syndrome.
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.
Martin-Moutot
Nicole
N
INSERM U641, Marseille F-13916, France. martin-moutot.n@jean-roche.univ.mrs.fr
Haro
Luc de
Ld
Santos
Raquel Gouvea Dos
RG
Mori
Yasuo
Y
Seagar
Michael
M
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D001667:Binding, Competitive / Q000276:immunology; D015220:Calcium Channels / Q000276:immunology*; D020864:Calcium Channels, N-Type / Q000276:immunology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D015624:Lambert-Eaton Myasthenic Syndrome / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000276:immunology; D009498:Neurotoxins; D011863:Radioimmunoassay / Q000379:methods*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013111:Spider Venoms; D013347:Subcellular Fractions / Q000276:immunology; D013570:Synaptic Membranes / Q000276:immunology; D020960:omega-Conotoxins
D001323:Autoantibodies; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D007457:Iodine Radioisotopes; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; D013111:Spider Venoms; D020960:omega-Conotoxins; C500963:Cacna1b protein, mouse