Martin-Moutot Nicole, Haro Luc de, Santos Raquel Gouvea Dos, Mori Yasuo, Seagar Michael
INSERM U641, Marseille F-13916, France.
Neurobiol Dis. 2006 Apr;22(1):57-63. doi: 10.1016/j.nbd.2005.10.003. Epub 2005 Nov 11.
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.
兰伯特-伊顿肌无力综合征（LEMS）是一种神经自身免疫性疾病，其中电压门控钙通道（VGCCs）下调导致运动神经元终末乙酰胆碱释放减少。70%的病例为副肿瘤性，快速诊断LEMS可实现对潜在肿瘤的早期检测。基于自身抗体沉淀放射性配体标记的VGCCs能力的血清学检测提供了有价值的数据。我们建立了一种使用蜘蛛毒液肽125I-ω-芋螺毒素IIA（125I-ωPtxIIA）的新型检测方法。125I-ωPtxIIA标记大鼠脑膜中的重组Cav2.1和Cav2.2通道以及内源性VGCCs。在26/31（84%）的LEMS患者中检测到能免疫沉淀125I-ωPtxIIA/通道复合物的自身抗体。125I-ωPtxIIA检测呈血清阳性的患者与使用两种不同的ω-芋螺毒素检测到的Cav2.1和/或Cav2.2抗体呈阳性的人群完全一致。因此，与目前基于ω-芋螺毒素的检测方法相比,125I-ωPtxIIA检测能检测到更广泛的自身抗体特异性。
