54:1107 自己免疫性脳炎は,急性・亜急性の経過で,頭痛,発熱, 興奮・健忘などの精神症状,意識障害,けいれんなどを呈し, 多くの例で神経細胞・グリア細胞の細胞膜上に発現する受容 体・チャネルに対する抗体を生じる.臨床的特徴が共通する ことが多く, 検索すべき抗体の選定に迷うことも少なくない. この中で,検出頻度が高いのは,抗電位依存性カリウムチャ ネル(voltage-gated potassium channel; VGKC)複合体抗体や 抗 N-methyl D-aspartate receptor(NMDAR)抗体がある.抗 体の検出は治療法選択に有用であるのみならず,症状の背景 となる病態を理解する上で重要である. NMDAR は,神経系の興奮性神経伝達物質であるグルタミ ン酸のイオンチャネル型受容体として,シナプス後膜表面に 発現する機能蛋白である.NMDA 受容体サブユニット GluN1 Autoimmune encephalitis is increasingly recognized having autoantibodies to synaptic cell

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... urface antigens, such as anti-N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated protein 1 (LGI1) by neurologists as well as pediatricians and psychiatrists, because these antibodies have been detected in cases of intractable epilepsy or atypical psychosis and in some demyelinating diseases, together with typical limbic encephalitis. Each group have characteristic clinical features, however, the disease spectrum has been expanding. To understand the significance of anti-NMDAR antibodies in the pathogenesis of NMDAR encephalitis, the role of the antibody in the disease process have been evaluated. The binding of antibody is shown to dimerize NMDARs and trigger their internalization on the postsynaptic site, thereby suppressing NMDAR-mediated transmission. To evaluate the antibody-induced dysfunction of NMDARs, we tested and showed the antibodies from the patients suppress the induction of NMDAR-dependent longterm potentiation (LTP) in mouse hippocampal slices. We also tested the antibody-effects on the cognitive functions of mice and revealed the CSF from NMDAR encephalitis patients had effects on disturbing spacial memory in mice. These results firmly support the proposal that the anti-NMDAR encephalitis autoantibody is responsible for cognitive disorders accompanying in this disease. (