結核病のリスクに対する血液RNAシグネチャー:前向きなコホート研究

Daniel E Zak¹, Adam Penn-Nicholson², Thomas J Scriba²

¹The Center for Infectious Disease Research, Seattle, WA, USA.

Lancet (London, England)

|March 28, 2016

まとめ

青少年や成人の肺結核の発症を予測できるのですこの発見は,世界的に結核と闘うための早期介入戦略の可能性を示しています.

科学分野:

ゲノミクス
感染症疫学
バイオマーカーの発見

背景:

結核 (TB) は世界的に大きな健康問題であり,早期発見方法が必要である.
Mycobacterium tuberculosisの感染から活性結核に進行するリスクのある個人を特定することは,効果的な介入に不可欠です.
現在の診断方法は病気を遅い段階で特定し予防の機会を制限しています

研究の目的:

全血の遺伝子発現が活性結核のリスクを予測する潜在的サインを特定できるかどうかを評価する.
結核リスク予測のための血液ベースの遺伝子発現シグネチャーを開発し,検証する.

主な方法:

M. 結核に感染した南アフリカの青少年 (12歳から18歳) の前向きなコホート研究.
血中RNAの配列解析により, リスクシグネチャーを特定し, 進行者と対照群を比較する.
青少年と独立した成人のコホートでの多重定量リアルタイムPCR (qRT-PCR) を使用してシグネチャの検証.

主要な成果:

全血RNAのシーケンシングデータから16遺伝子のリスクシグネチャーが特定されました.
このシグネチャーは,青少年における診断前の12ヶ月間に結核の進行を予測する中等感度 (66. 1%) と良好な特異性 (80. 6%) を示した.
このシグネチャーは,未接触の青少年サンプルと独立した南アフリカおよびガンビアの成人のコホートで成功裏に検証され,有意な予測値 (p<0. 018) を示した.

結論:

全血遺伝子発現シグネチャーは,活性結核を発症するリスクのある個人を将来的に特定することができます.
この発見は結核の進行を防ぐための標的型介入の道を開きます
検証されたサインはリスク集団における早期のリスク評価に期待を寄せています

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