多発性硬化症のB細胞は,EBV EBNA1とGlialCAMと結合する

Tobias V Lanz^1,2,3,4, R Camille Brewer^1,4, Peggy P Ho⁵

¹Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Nature

|January 24, 2022

まとめ

エプスタイン・バーウイルス (EBV) と多発性硬化症 (MS) を結びつけるのは分子模倣メカニズムです EBVを標的とする抗体

科学分野:

神経免疫学
ウイルス学
分子模倣法

背景:

多発性硬化症 (MS) は中枢神経系を標的とした自己免疫疾患です.
脳脊髄液 (CSF) のB細胞は,MSの炎症に寄与する.
エプスタイン・バーウイルス (EBV) は流行病学的にMSと関連しているが,その役割は不明である.

研究の目的:

EBVとMSを結びつける分子メカニズムを調査する
EBVと中枢神経系タンパク質の交互反応性抗体を特定する
MSの病原性における分子模倣の構造的および機能的証拠を提供すること.

主な方法:

MS患者のB細胞の単細胞配列解析
ウイルス抗原に対するCSF由来抗体のタンパク質マイクロアレイ検査
EBNA1-GlialCAM エピトープ-抗体複合体の結晶構造の決定
MSのマウスモデルを用いた in vivo 研究

主要な成果:

EBVのEBNA1とGlialCAMの間の高親和分子ミミクリが確認されました.
分子模倣による抗体の交叉反応が示された.
EBNA1免疫はマウスモデルでMSを悪化させることが示された.
多発性硬化症患者の抗EBNA1および抗GlialCAM抗体の有病率が見つかりました.

結論:

EBV感染とMSの病原性との間にメカニズム的な関連が確立された.
EBNA1とGlialCAMの間の分子模倣は重要な要因である.
発見は,MSの新たな治療戦略に役立つかもしれません.

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