検査と技術51巻9号

2023年09月発行

増大号 匠から学ぶ　血栓止血検査ガイド 5章　疾患まとめ

発作性夜間ヘモグロビン尿症（PNH）と血栓症

著者： 高森弘之¹ 西村純一²

所属機関： ¹東京大学医科学研究所造血病態制御学分野 ²大阪大学大学院医学系研究科血液・腫瘍内科

ページ範囲：P.1145 - P.1150

はじめに

　発作性夜間ヘモグロビン尿症（paroxysmal nocturnal hemoglobinuria：PNH）は，PIGA（phosphatidylinositol glycan anchor biosynthesis class A）遺伝子変異による造血器クローン疾患であり，血管内溶血，血栓症，骨髄不全症が特徴的な臨床症状である^1）．PIGA遺伝子は，GPIアンカー型タンパク質（glycosylphosphatidylinositol-anchored proteins：GPI-APs）の生合成に関与し，機能喪失型の遺伝子変異が生じると，GPI-APsの生合成が阻害される．CD55/59は，赤血球で補体制御の中心的役割を果たすGPI-APsである．PIGA遺伝子変異が生じた造血幹細胞レベルの細胞から分化したPNH赤血球はCD55/59を欠損するため，補体経路の活性化により溶血し，PNHのさまざまな臨床症状を引き起こす．PIGA遺伝子変異により生じたPNHクローンが拡大しなければ臨床症状は顕在化しないが，拡大機序はいまだ十分に解明されていない．

　血栓症はPNHにおいて最も重篤な臨床症状の1つである．抗補体薬であるエクリズマブ（eculizumab：ECU）の登場により血栓症のリスクが改善されたことから，補体経路と血栓症の関連が示唆されている^2）．抗補体薬によりPNHの臨床成績は著しく改善してきているが，それでもなおPNH診療において血栓症は最も注意が必要な合併症の1つである．

参考文献

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