Identification of auto-antigens in acquired aplastic anemia associated with clonal hematopoiesis by hematopoietic stem cells with uniparental disomy of chromosome 6p

6p染色体单亲二体性造血干细胞克隆性造血相关获得性再生障碍性贫血自身抗原的鉴定

• 批准号: 23659486
• 负责人: NAKAO Shinji
• 金额: $ 2.41万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 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-23659486/
• 关键词: 再生不良性貧血; 6pLOH; 自己抗原; CLT; HLA-B*40:02; CTL; 肝炎関連再生不良性貧血; HLA; 片親性二倍体; 抗HLA抗体

To determine the exact prevalence of HLA-A allele-lacking leukocytes (HLA-LLs) in patients with acquired aplastic anemia (AA), we improved the sensitivity of flow cytometry and examined peripheral blood leukocytes of patients with newly-diagnosed AA patients. HLA-LLs were detectable in 6 (28.6%) of 21 patients who were heterozygous with the HLA-A allele. The percentage of HLA-A allele-lacking granulocytes in the total granulocytes ranged from 3.9% to 61.1% (median 8.4%), which was lower than that in patients in remission after immunosuppressive therapy. Cytotoxic T cell (CTL) clones (A6) were successfully established from one of the patients possessing HLA-LLs by stimulating patient’s CD8+T cells with K562 cells transfected with HLA-B*40:02 gene. A6 CTL killed K562 in B*40:02 restricted manner but did not kill other cells including EB virus-transformed lymphoblastoid cell line and Jurkat T cell line transduced with B*40:02.

为了确定获得性再生障碍性贫血(AA)患者中人类白细胞抗原-A等位基因缺失(HL A-LLS)的确切患病率，我们改进了流式细胞术的灵敏度，并检测了新诊断的AA患者的外周血白细胞。21例人类白细胞抗原A等位基因杂合子患者中，6例(28.6%)可检出HL A-LLS。HLAA等位基因缺失的粒细胞占粒细胞总数的比例为3.9%~61.1%(中位数8.4%)，低于免疫抑制治疗后缓解组。用人类白细胞抗原B*40：02基因修饰的K562细胞刺激CD8+T细胞，从1例具有人类白细胞抗原-LLS的患者体内成功建立了细胞毒性T细胞克隆(A6)。A6CTL以B*40：02限制性方式杀伤K562细胞，对EB病毒转化的淋巴母细胞系和转导B*40：02的Jurkat T细胞系无杀伤作用。

项目成果

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

• DOI: 10.3324/haematol.2012.066217
• 发表时间: 2013-06-01
• 期刊: HAEMATOLOGICA
• 影响因子: 10.1
• 作者: Seiki, Yu;Sasaki, Yumi;Nakao, Shinji
• 通讯作者: Nakao, Shinji

Frequent loss of HLA alleles from hematopoietic stem cells in patients with hepatitis-associated aplastic anemia.

肝炎相关再生障碍性贫血患者的造血干细胞中 HLA 等位基因经常丢失。

• 作者: Takamasa Katagiri;Aiko Sato-Otsubo;Koichi Kashiwase;Satoko Morishima;Yusuke Sato;Yuka Mori;Motohiro Kato;Masashi Sanada;Yasuo Morishima;Shigeki Ohtake;Seishi Ogawa;Shinji Nakao
• 通讯作者: Shinji Nakao

Aplastic anemia successfully treated with rituximab: the possible role of aplastic anemia-associated autoantibodies as a marker for response

利妥昔单抗成功治疗再生障碍性贫血：再生障碍性贫血相关自身抗体作为反应标志物的可能作用

• DOI: 10.1111/j.1600-0609.2011.01612.x
• 发表时间: 2011
• 期刊: Eur J Haematol
• 影响因子: 3.1
• 作者: Takamatsu H.;Yagasaki H.;Takahashi Y.;Hama A.;Saikawa Y.;Yachie A.;Koizumi S.;Kojima S.;Nakao S
• 通讯作者: Nakao S

An Epstein-Barr Virus-Associated Leukemic Lymphoma in a Patient Treated with Rabbit Antithymocyte Globulin and Cyclosporine for Hepatitis-Associated Aplastic Anemia

• DOI: 10.1159/000333609
• 发表时间: 2012-01-01
• 期刊: ACTA HAEMATOLOGICA
• 影响因子: 2.4
• 作者: Ohata, Kinya;Iwaki, Noriko;Nakao, Shinji
• 通讯作者: Nakao, Shinji

Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia

• DOI: 10.1182/blood-2011-07-365189
• 发表时间: 2011-12-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Katagiri, Takamasa;Sato-Otsubo, Aiko;Nakao, Shinji
• 通讯作者: Nakao, Shinji