Identification of auto-antigens which trigger the development of immune-mediated bone marrow failure

鉴定引发免疫介导的骨髓衰竭发展的自身抗原

• 批准号: 21390291
• 负责人: NAKAO Shinji
• 金额: $ 11.56万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390291/
• 关键词: 再生不良性貧血; 6pUPD; HLA; 細胞傷害性T細胞; 自己抗原; GPIアンカー膜蛋白; PNH; TGF-β; CD109; 骨髄不全; 自己抗体; PNH型血球; GPI-アンカー膜蛋白; 13q-; RB遺伝子

Genomic analyses of patients with acquired aplastic anemia(AA) revealed the presence of leukocytes lacking an HLA haplotype as a result of uniparental disomy of chromosome 6p in 13% of patients. The missing HLA haplotypes were strongly biased to HLA-A^* 02 : 01, A^* 02 : 06, A^* 31 : 01, and B^* 40 : 02, which were over-represented in Japanese AA cases. Cytotoxic T lymphocytes specific to hematopoietic stem cell-derived auto-antigens presented by the particular HLAs was thought to trigger the development of AA.

对获得性再生障碍性贫血 (AA) 患者的基因组分析显示，13% 的患者由于 6p 染色体单亲二体性而存在缺乏 HLA 单倍型的白细胞。缺失的 HLA 单倍型强烈偏向于 HLA-A^* 02 : 01、A^* 02 : 06、A^* 31 : 01 和 B^* 40 : 02，这些在日本 AA 病例中比例过高。特定 HLA 呈递的造血干细胞衍生自身抗原特异的细胞毒性 T 淋巴细胞被认为可触发 AA 的发生。

项目成果

PNH型白血球の検出方法

如何检测PNH型白细胞

• 发表时间: 2010

Bone marrow failure with 13q deletion : A distinct clinicopat hological entity with immune pathophysiology

13q 缺失引起的骨髓衰竭：具有免疫病理生理学的独特临床病理学实体

• 发表时间: 2011
• 作者: Kohei Hosokawa;Takamasa Katagir;Naomi Sugimori;Ken Ishiyama;Yumi Sasaki;Yu Seiki;Aiko Sato-Otsubo;Masashi Sanada;MD;Seishi Ogawa;Shinji Nakao
• 通讯作者: Shinji Nakao

GPI-AP deficient cells detected exclusively in T cells in patients with aplastic anemia : Evidence against an escape mechanism for the initial proliferation of PIGA mutant hematopoietic stem cells

仅在再生障碍性贫血患者的 T 细胞中检测到 GPI-AP 缺陷细胞：反对 PIGA 突变造血干细胞初始增殖逃逸机制的证据

• 发表时间: 2009
• 作者: Katagiri;T.;Qi;Z.;Seiki;Y.;Sugimori;N.;Espinoza;J;L.;Takami;A.;Ohtake;S.;Nakao;S.
• 通讯作者: S.

Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure

• DOI: 10.1111/j.1365-2141.2009.07822.x
• 发表时间: 2009-10-01
• 期刊: BRITISH JOURNAL OF HAEMATOLOGY
• 影响因子: 6.5
• 作者: Sugimori, Chiharu;Mochizuki, Kanako;Nakao, Shinji
• 通讯作者: Nakao, Shinji

Immunologically-Selected Hematopoiesis Caused by HLA Allelic Loss In Patients with Aplastic Anemia

再生障碍性贫血患者 HLA 等位基因缺失引起的免疫选择造血

• 发表时间: 2010
• 作者: Katagiri;T.;Matsubara;A.;Kashiwase;K.;Kato;M.;Morishima;Y.;Hosokawa;K.;Ohtake;S.;Ogawa;S.;Nakao;S.
• 通讯作者: S.