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BRAIN and NERVE Volume 70, Issue 4 （April 2018）

BRAIN and NERVE 70巻4号（2018年4月発行）

Japanese English

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 Current Perspective on Voltage-gated Potassium Channel Complex Antibody Associated Diseases 渡邊修 ¹ Osamu Watanabe ¹ ¹鹿児島市立病院神経内科 ¹Division of Neurology, Kagoshima City Hospital キーワード： VGKC複合体抗体 , LGI1抗体 , Caspr2抗体 , 病態関連抗体 , 細胞内ドメインに対する抗体 , leucine rich glioma inactivated protein 1 antibody , LGI1 antibody , contactin associated protein 2 antibody , Caspr2 antibody , faciobrachial dystonic seizuires , FBDS , pathogenic antibody , intracellular domain Keyword: VGKC複合体抗体 , LGI1抗体 , Caspr2抗体 , 病態関連抗体 , 細胞内ドメインに対する抗体 , leucine rich glioma inactivated protein 1 antibody , LGI1 antibody , contactin associated protein 2 antibody , Caspr2 antibody , faciobrachial dystonic seizuires , FBDS , pathogenic antibody , intracellular domain pp.315-328

発行日 2018年4月1日 Published Date 2018/4/1

DOI https://doi.org/10.11477/mf.1416201005

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参考文献 Reference

電位依存性カリウムチャネル（VGKC）複合体抗体は，アイザックス症候群，モルヴァン症候群，さらに近時記憶障害とてんかんを主張とする辺縁系脳炎の病態関連抗体である。VGKC複合体の主要抗原はLGI1（leucine-rich glioma inactivated protein 1）とCaspr2（contactin-associated protein 2）である。これらに対する抗体が陰性の場合，VGKC複合体抗体が細胞内ドメインに反応しており，病態には直接関連はない。

Abstract

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.