NKG2D-mediated immunity in bone marrow failure syndromes

NKG2D 介导的骨髓衰竭综合征免疫

• 批准号: 23791087
• 负责人: HANAOKA Nobuyoshi
• 金额: $ 2.75万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791087/
• 关键词: 特発性造血障害; NKG2D免疫; PNH; 内科; 免疫学; NKG2D; 造血障害

Acquired idiopathic bone marrow failure responds to immunosuppressive therapy (IST), indicating that marrow failure is immune-mediated. However, molecular pathogenesis of the immune, including on hematopoietic progenitor cells,is unknown. In the present study, we show that NKG2D-mediated immunity closely links with marrow injury in a patient with paroxysmal nocturnal hemoglobinuria. We found both that NKG2D ligands including ULBP and MICA/B were pathologically expressed on granulocytes, whereas NKG2D receptor on lymphocytes of the patient, and that IST was effective for the marrow failure. We then propose that NKG2D-mediated immunity could directly visualizeimmune condition of the marrow failure. Currently, we are confirming the NKG2D-associated immunity decides the timing of discontinuation of IST in the patient.ient.

获得性特发性骨髓衰竭对免疫抑制治疗（IST）有反应，表明骨髓衰竭是免疫介导的。然而，免疫的分子发病机制，包括造血祖细胞的分子发病机制，尚不清楚。在本研究中，我们发现 NKG2D 介导的免疫与阵发性睡眠性血红蛋白尿症患者的骨髓损伤密切相关。我们发现包括 ULBP 和 MICA/B 在内的 NKG2D 配体在粒细胞上病理性表达，而 NKG2D 受体在患者的淋巴细胞上表达，并且 IST 对骨髓衰竭有效。然后我们提出 NKG2D 介导的免疫可以直接可视化骨髓衰竭的免疫状况。目前，我们正在确认 NKG2D 相关的免疫决定了患者停止 IST 的时间。

项目成果

Pathophysiology of extravascular hemolysis in paroxysmal nocturnal hemoglobinuria

阵发性睡眠性血红蛋白尿症血管外溶血的病理生理学

• 发表时间: 2012
• 作者: Hanaoka N; Murakami Y; Nagata M; Nagakura S; Yonemura Y; Sonoki T; Kinoshita T; Nakakuma H.
• 通讯作者: Nakakuma H.

Occupancy of whole blood cells by a single PIGA-mutant clone with HMGA2 amplification in a paroxysmal nocturnal haemoglobinuria patient having blood cells with NKG2D ligands

在具有带有 NKG2D 配体的血细胞的阵发性睡眠性血红蛋白尿症患者中，具有 HMGA2 扩增的单一 PIGA 突变克隆对全血细胞的占据

• DOI: 10.1111/bjh.12093
• 发表时间: 2013
• 作者: Hanaoka; N.; Y. Murakami; M. Nagata; K. Horikawa; S. Nagakura; Y. Yonemura; S. Murata; T. Sonoki; T. Kinoshita; H. Nakakuma
• 通讯作者: H. Nakakuma