ナルコレプシー患者のT細胞は,ヒポクレチンニューロンの自己抗原を標的にする

Daniela Latorre^1,2, Ulf Kallweit^3,4, Eric Armentani¹

¹Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland.

Nature

|September 21, 2018

まとめ

麻酔は自己免疫疾患でヒポクレチンニューロンの減少が原因です研究者らはナルコレプシー患者で低クレチン特異性T細胞を発見しこの慢性睡眠障害の自己免疫的原因を確認しました

科学分野:

神経免疫学
睡眠医学
自己免疫性

背景:

ナルコレプシは慢性的な睡眠障害でヒポクレチン産生ニューロンの喪失と関連しています
証拠は自己免疫的起源を示唆しているが,自己反応性リンパ球の直接的な証拠は限られている.

研究の目的:

ナルコレプシー患者の自己反応性T細胞の存在と特徴を調査する.
ナルコレプシーの原因を証明する細胞の証拠を提供するためです

主な方法:

敏感な細胞スクリーンを用いて,ヒポクレチン特異のCD4+およびCD8+T細胞を検出した.
分析されたT細胞特異性,エピトープターゲティング,HLA制限,インフルエンザ抗原との交叉反応性.

主要な成果:

検査されたすべてのナルコレプシー患者において,ヒポクレチン特異性CD4+T細胞が検出されました.
他のヒポクレチンニューロン抗原 (トリブルスホモログ2) を標的にするT細胞は,大部分の患者で発見されました.
自主反応性T細胞はポリクローンで,複数のエピトープを標的とし,主にHLA- DRに制限され,インフルエンザ抗原に対するクロス反応性は認められなかった.
血液と脳脊髄液でヒポクレチン特異性CD8+T細胞が検出されました.
自己反応性クローン型は患者では連続的に検出されたが,健康な対照群では検出されなかった.

結論:

これらの発見は,ナルコレプシーにおける自己免疫的原因の強力な証拠を提供します.
特定の自己反応性T細胞の特定は,ナルコレプシーの改善された診断と潜在的な治療戦略の基盤を提供します.

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