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%的患者由于染色体6p的单亲二倍体而存在缺乏HLA单倍型的白细胞。缺失的单倍型倾向于在日本再生障碍性贫血病例中过度表达的人类白细胞抗原-A^*02：01、A^*02：06、A^*31：01和B^*40：02。由特定的HLA呈递的针对造血干细胞来源的自身抗原的细胞毒性T淋巴细胞被认为触发了再障的发生。

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

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.

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

Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma.

再生障碍性贫血患者血清中的抗肌蛋白抗体刺激外周血单核细胞分泌TNF-α和IFN-γ。

• 发表时间: 2009
• 期刊: J Immunol 182
• 作者: Takamatsu H;et al
• 通讯作者: et al

A Functional variation in the NKG2D gene regulates NKG2D receptor expression and is associated with better transplant outcomes after fully-HLA-macthed unrelated bone marrow transplantation

NKG2D 基因的功能变异可调节 NKG2D 受体表达，并与完全 HLA 匹配的无关骨髓移植后更好的移植结果相关

• 发表时间: 2010
• 作者: J;Luis;Espinoza.;Takami;A.;Yoshioka;K.;Nakata;K.;Nakao;S.
• 通讯作者: S.