GABAa受体抗体与癫痫,癫痫持续状态和删除从突触受体(P3.001)

文摘

目的:报告识别与GABAa受体相关的小说综合症(GABAaR)抗体和病人的抗体对神经元的影响文化。背景:有证据表明,癫痫发作和癫痫持续状态可以从突触自身免疫结果。GABAaR没有先前报道为自身免疫的目标。方法:140例的血清或脑脊液脑炎、癫痫发作和癫痫持续状态,未知抗原的抗体对抗原特征选择。技术包括免疫沉淀反应、质谱分析、细胞分析(CBA),抗体的影响分析的基础上培养的大鼠海马神经元。七十五正常受试者和416名患者从几个组织疾病作为控制。结果:神经细胞表面免疫沉淀反应显示GABAaR序列。CBAα1和/或β3 GABAaR的子单元显示high-titer血清抗体(> 1:160)和脑脊液抗体在6/140的病人。所有6例(3 - 63岁,平均22;5男)开发了难治性癫痫持续状态/ epilepsia partialis连续连同广泛cortical-subcortical MRI异常; four patients required pharmacologically-induced coma. Twelve/416 patients from disease-group controls, but none of the healthy group, had low-titer GABAaR antibodies only in serum, 5 along with GAD65 antibodies. These 12 patients (2-74 year, median 26.5; 7 male) developed a broader spectrum of symptoms likely reflecting coexisting autoimmunities: 6 had encephalitis with seizures (1 with status epilepticus/pharmacological coma; 1 epilepsia partialis continua), 4 stiff-person syndrome (1 with seizures), and 2 opsoclonus-myoclonus. Overall, 12/15 assessable patients had full (3) or partial (9) response to treatment, and three died. Patient’s antibodies caused a selective reduction of GABAaR clusters at synapses, but not along dendrites, without altering gephyrin (a protein that anchors GABAaR). Conclusions: High-titer GABAaR antibodies associate with a severe form of encephalitis with seizures and/or refractory status epilepticus. The antibodies cause a selective reduction of synaptic GABAaR. The disorder frequently occurs with gabaergic and other co-existing autoimmunities and is potentially treatable. Study Supported by Instituto Carlos III, FI12/00366, FIS PI11/01780, and PI12/00611, and the National Institutes of Health RO1NS077851, MH094741 and Fundació la Marató TV3 (101530)

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