Phoneutria nigriventer ω-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-ω-Phonetoxin IIA (125I-ωPtxIIA). 125I-ωPtxIIA labeled recombinant Cav2.1 and Cav2.2 channels and endogenous VGCCs in rat brain membranes. Autoantibodies that immunoprecipitate a 125I-ωPtxIIA/channel complex were detected in 26/31 (84%) LEMS patients. The patients that were seropositive in the 125I-ωPtxIIA assay corresponded precisely to the population that was positive for Cav2.1 and/or Cav2.2 antibodies detected using two different ω-conotoxins. Thus, the 125I-ωPtxIIA assay detects a broader spectrum of autoantibody specificities than current ω-conotoxin-based assays.

Keywords

• Lambert–Eaton myasthenic syndrome
• ω-Phonetoxin IIA
• Calcium channel
• Serological assay
• Autoantibodies