BRAIN and NERVE－神経研究の進歩64巻5号

2012年05月発行

特集 神経疾患のバイオマーカー

視神経脊髄炎のバイオマーカー

著者： 三須建郎¹² 高橋利幸³ 中島一郎¹ 藤原一男¹²

所属機関： ¹東北大学医学部神経内科 ²東北大学医学部多発性硬化症治療学 ³独立行政法人国立病院機構米沢病院神経内科

ページ範囲：P.525 - P.535

文献概要

はじめに

　視神経脊髄炎（neuromyelitis optica：NMO）は，1894年のDevicらによる研究に端を発した中枢神経系の炎症性疾患であり，多発性硬化症（multiple sclerosis：MS）との異同が繰り返し論じられてきた^1,2)。病理学的には灰白質病変が多いこと，壊死性変化がMSより強く，時に著しい脊髄の萎縮をきたすことなどが知られ，NMOの特徴として考えられてきた歴史がある²⁾。

　1999年にWingerchukら³⁾はメイヨー・クリニックで経験された71例のNMO患者を検証し，MSとは異なるNMOの特徴として，初期の脳MRI病変の欠如，髄液中細胞数の増加（＞50/μL）や3椎体以上に及ぶ脊髄病変を報告した。NMOでは，脳病変が少ないこと，長い脊髄病変や横断性脊髄炎を有すること，MSの診断マーカーとして利用されてきたオリゴクローナルバンドの検出率が極めて低いということ，自己抗体を有する割合が多いこと，圧倒的に女性が多いことなどが知られていた^4-6)。このような臨床的指標のそれぞれもまた，NMOの特徴として認識されてきた。

　NMOに特異的な自己抗体であるNMO-IgGの発見によって，NMOの日常診療は大きく変わった⁷⁾。現在は，HEK293T細胞などを用いたヒトアクアポリン4（aquaporin 4：AQP4）特異的抗体の検出法やenzyme-linked immunosorbent assay（ELISA）法などが開発され，感度・特異度には違いがあるものの，おおよそ70％前後の感度と90％以上の特異度をもって国際的にNMOの診断が行われるようになっている⁸⁾。NMO-IgGは診断だけではなく治療の選択においても非常に重要な意味がある。NMO-IgG陽性例ではMSで第一選択薬として使われてきたインターフェロン（interferon：IFN）療法ではかえって病態を悪化させる症例が多く，初めに選択すべき治療ではないことは既に周知された事実である^9-12)。また，AQP4抗体以外にもNMOの臨床病勢や免疫病態を理解するうえでの有用なバイオマーカーが数々報告されるようになってきている。

　本稿では，NMOの診断や治療などについては他の優れた文献に譲り，近年問題となっているAQP4抗体の検査法や神経傷害マーカーとしてのアストロサイト関連マーカーの意義，病態を反映する数々のサイトカインなどに焦点を当てることとする。

参考文献

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