VGKC関連抗体

VGKC-Complex Antibodies

はじめに

　電位依存性カリウムチャネル（voltage-gated potassium channel：VGKC）関連抗体の代表的なものは，VGKCのリガンドである¹²⁵I-αデンドロトキンを用いたRIA（radioimmunoassay）法により検出される抗VGKC複合体抗体である。この抗体は，以前は，単に「抗VGKC抗体」と称されていたが，その後の研究でVGKCそのもののみならず，VGKCと複合体を形成する種々の分子に対する抗体を網羅するものであることが最近の研究で明らかになった（Table1）。

　このRIA法によるスクリーニング検査で検出されないVGKCに関連する新たな抗体の報告もあるが¹⁾，本稿では，抗VGKC複合体抗体を中心に取り上げ，作用機序や疾患との関連性について概説する。また，てんかんや疼痛との関連や，クロイツフェルト・ヤコブ病（Creutzfeldt-Jakob disease：CJD）や筋萎縮性側索硬化症（amyotrophic lateral sclerosis：ALS）と本抗体との関連性についても触れてみたい。

Abstract

　Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated.

　These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).