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生体肝移植グラフト質的評価マーカーとしてのLRRN2発現上昇

冨山, 貴央 TOMIYAMA, Takahiro トミヤマ, タカヒロ 九州大学

2022.09.22

概要

【背景】生体肝移植(living donor liver transplantation: LDLT)においてグラフトの質と大きさはグラフト機能とレシピエントの予後に影響する重要な因子である。しかし、グラフトの質的評価を行う因子はよくわかっておらず、現在汎用されているグラフト質的評価マーカーはドナーの年齢のみである。ドナー年齢とは別に、独自のグラフト質的評価マーカーを特定するために、カニクイザルの肝組織を利用し、本研究を行った。

【方法・結果】若年および高齢のカニクイザルの肝臓遺伝子マイクロアレイ発現データから、高齢群で発現が有意に増加する遺伝子が合計271個あることが判明した。これらの候補遺伝子は、バイオインフォマティクス解析により6個に絞り込まれた。続いて、これらの候補遺伝子のヒトドナー肝組織における発現パターンを検討した。重要なことは、これら6つの候補遺伝子の発現が上昇しているグラフトは、早期グラフト不全の発生率が上昇していた。さらに多変量解析により、ドナー肝組織におけるLRRN2(encording leucine-rich repeat protein, neuronal2)の発現上昇が、早期グラフト不全の独立した危険因子であることが明らかになった(オッズ比4.50、信頼区間2.08-9.72)。グラフトのLRRN2の発現とドナーの年齢に基づく層別化も、6カ月間のグラフト生存率と有意に関連していた。

【結語】グラフトにおけるLRRN2発現の上昇は、LDLTにおける早期グラフト不全と有意に相関する。さらに、グラフトLRRN2発現とドナー年齢の組み合わせは、LDLTグラフト品質を予測するための有用なマーカーとなりうる。

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