増大特集 Antibody Update 2018 電位依存性カリウムチャネル(VGKC)複合体抗体関連疾患up to date
増大特集 Antibody Update 2018 電位依存性カリウムチャネル(VGKC)複合体抗体関連疾患up to date
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增加特殊功能抗体更新 2018 电压门控钾通道 (VGKC) 复合物抗体相关疾病最新
DOI：
10.11477/mf.1416201005
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
渡邊 修
中科院分区：
文献类型：
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作者：
Ohyama K;Koike H;Hashimoto R;Takahashi M;Kawagashira Y;Iijima M;Katsuno M;Sobue G.;飯島正博;渡邊 修
电压门控性钾通道(VGKC)复合体自身抗体最初在以肌肉痉挛和神经性肌强直为特征的Isaacs综合征(IS)中被发现。这些抗体随后在Morvan‘s综合征(MoS)患者中被发现，该综合征包括与精神病、失眠和自主神经功能障碍相关的IS。在一名边缘脑病(LE)患者中也检测到了这种抗体，该患者表现为明显的健忘和频繁的癫痫发作。典型的LE病例起病于成人，伴有频繁、短暂的肌张力障碍发作，主要累及手臂和同侧面部，最近被称为面臂肌张力障碍发作。在IS、MoS和LE患者中，存在针对VGKC复合体蛋白胞外区的自身抗体，即富含亮氨酸的胶质瘤灭活1(LGI1)和接触素相关蛋白2(Caspr2)。然而，常规检测在其他疾病患者中检测到没有LGI1或Caspr2反应的VGKC复合抗体(双阴性)，如克雅氏病和肌萎缩侧索硬化症。此外，双阴性的VGKC复合体抗体通常针对KV1亚基的胞浆表位。因此，这些抗体不应再被归类为神经元表面抗体，缺乏致病潜力。关于自身抗体破坏靶蛋白的生理功能的新信息已经产生。LGI1抗体中和了LGI1和ADAM22之间的相互作用，从而减少了突触AMPA受体。这可能是主要作用于抑制性神经元，解释了为什么AMPA受体的缺失会导致失忆、神经元兴奋性和癫痫发作。
Voltage-gated potassium channel (VGKC) complex auto-antibodies were initially identified in Isaacs' syndrome (IS), which is characterized by muscle cramps and neuromyotonia. These antibodies were subsequently identified in patients with Morvan's syndrome (MoS), which includes IS in conjunction with psychosis, insomnia, and dysautonomia. The antibodies have also been detected in a patient with limbic encephalopathy (LE) presenting with prominent amnesia and frequent seizures. Typical cases of LE have adult-onset, with frequent, brief dystonic seizures that predominantly affect the arms and ipsilateral face, and has recently been termed faciobrachial dystonic seizures. Autoantibodies against the extracellular domains of VGKC complex proteins, leucine-rich glioma-inactivated 1 (LGI1), and contactin-associated protein-2 (Caspr2), occur in patients with IS, MoS, and LE. However, routine testing has detected VGKC complex antibodies without LGI1 or Caspr2 reactivities (double-negative) in patients with other diseases, such as Creutzfeldt-Jakob disease and amyotrophic lateral sclerosis. Furthermore, double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits. Therefore, these antibodies should no longer be classified as neuronal-surface antibodies and lacking pathogenic potential. Novel information has been generated regarding autoantibody disruption of the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, thereby reducing the synaptic AMPA receptors. It may be that the main action is on inhibitory neurons, explaining why the loss of AMPA receptors causes amnesia, neuronal excitability and seizures.