Analysis of mechanisms responsible for clonal expansion of PNH-type hematopoietic stem cells mediated by autoreactive T cells in patients with bone marrow failure
骨髓衰竭患者自身反应性T细胞介导的PNH型造血干细胞克隆扩增机制分析
基本信息
- 批准号:17390275
- 负责人:
- 金额:$ 9.79万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2005
- 资助国家:日本
- 起止时间:2005 至 2006
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In an attempt to determine whether CD4^+ T cells specific to diazepam-binding inhibitor protein-1 (DRS-1) contribute to the survival advantage of paroxysmal nocturnal hemoglobinuria (PNH)-type stem cells, we established a lymphobastoid cell line with PIG-A mutation from an aplastic anemia (AA) patients showing a high titer antibodies speicific to DRS-1. We tried to transfect the PNH-type LCL cells with DRS-1 cDNA using various methods such as retroviral vectors and electroporation to use them as a target of DRS-1 specific CD4^+ T cells. However, all the methods failed to induce expression of DRS-1 gene in LCL cells, probably due to inhibitory mechanisms for the DRS-1 expression inherent to B lymphocytes. Thus, we suspended this experiments and focused on another candidate autoantigen, moesin.We screened the sera of AA patients possessing small populations of PNH-type cells for the presence of antibodies (Abs) which recognize proteins derived from a leukemia cell line, UT-7. Immunoblott … More ing using proteins derived from lysates or culture supernatants of UT-7 cells revealed the presence of IgG Abs specific to an 80 kD protein. Peptide mass fingerprinting identified this 80 kD protein as moesin. Enzyme-linked immunosorbent assay (ELISA) using recombinant moesin showed high titers of anti-moesin Abs in 25 (37%) of 67 AA patients. Moesin was secreted from several myeloid leukemia cell lines other than UT-7, such as OUN-1 and K562, as an exosomal protein. The presence of anti-moesin Abs was significantly correlated with the presence of PNH-type cells and anti-diazepam-binding inhibitor-related protein-1 (DRS-1) Abs. AA patients that did not show any of these three markers tended to respond poorly to immunosuppressive therapy. These findings suggest that a B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with AA and that detection of anti-moesin Abs in combination with other markers may be useful in diagnosing immune pathophysiology in AA patients. Less
为了确定CD4^+ T细胞对地西潘结合抑制剂蛋白-1 (DRS-1)的特异性是否有助于突发性夜间血红蛋白尿(PNH)型干细胞的生存优势,我们从再生障碍性贫血(AA)患者中建立了具有猪- a突变的淋巴样细胞系,该细胞系显示出对DRS-1的高滴度抗体。我们尝试用逆转录病毒载体和电穿孔等多种方法转染pnh型LCL细胞,将其作为DRS-1特异性CD4^+ T细胞的靶细胞。然而,所有方法均未能诱导LCL细胞中DRS-1基因的表达,这可能与B淋巴细胞固有的抑制DRS-1表达的机制有关。因此,我们暂停实验,专注于另一种候选自身抗原moesin。我们筛选了拥有少量pnh型细胞的AA患者血清中存在的抗体(Abs),这些抗体可识别来自白血病细胞系UT-7的蛋白质。免疫印迹:使用UT-7细胞裂解液或培养上清液中提取的蛋白质进行更多的检测,发现存在针对80 kD蛋白的IgG抗体。肽质量指纹图谱鉴定该80 kD蛋白为moesin。重组moesin酶联免疫吸附试验(ELISA)显示,67例AA患者中25例(37%)抗moesin抗体滴度高。Moesin作为外泌体蛋白从除UT-7以外的几种髓系白血病细胞系(如OUN-1和K562)中分泌。抗moesin抗体的存在与pnh型细胞和抗地西泮结合抑制剂相关蛋白-1 (DRS-1)抗体的存在显著相关。未显示这三种标志物的AA患者对免疫抑制治疗的反应往往较差。这些发现表明,b细胞对moesin的反应,可能来源于造血细胞,经常发生在AA患者中,检测抗moesin抗体结合其他标志物可能有助于诊断AA患者的免疫病理生理。少
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia
- DOI:10.1182/blood-2005-06-2485
- 发表时间:2006-02-15
- 期刊:
- 影响因子:20.3
- 作者:Sugimori, C;Chuhjo, T;Nakao, S
- 通讯作者:Nakao, S
Roles of DRB1*1501 and DRB1*1502 in the pathogenesis of aplastic anemia
- DOI:10.1016/j.exphem.2006.09.002
- 发表时间:2007-01-01
- 期刊:
- 影响因子:2.6
- 作者:Sugimori, Chiharu;Yamazaki, Hirohito;Nakao, Shinji
- 通讯作者:Nakao, Shinji
Reduced-intensity unrelated cord blood transplantation for treatment of metastatic renal cell carcinoma : first evidence of cord-blod-versus-solid-tumor effect.
降低强度无关脐带血移植治疗转移性肾细胞癌:脐带血与实体瘤效应的第一个证据。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Takami;A.;et al.
- 通讯作者:et al.
Reduced-intensity unrelated cord blood transplantation for treatment of metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor effect.
降低强度无关脐带血移植治疗转移性肾细胞癌:脐带血与实体瘤效应的第一个证据。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Takami A;et. al.
- 通讯作者:et. al.
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NAKAO Shinji其他文献
NAKAO Shinji的其他文献
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{{ truncateString('NAKAO Shinji', 18)}}的其他基金
Identification of autoantigens presented by specific HLA class I alleles in aplastic anemia
再生障碍性贫血中特定 HLA I 类等位基因呈现的自身抗原的鉴定
- 批准号:
19H03686 - 财政年份:2019
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of cytokines responsible for the development of immune-mediated bone marrow failure using gene expression analyses of patients with aplastic anemia
利用再生障碍性贫血患者的基因表达分析来鉴定导致免疫介导的骨髓衰竭发生的细胞因子
- 批准号:
25670448 - 财政年份:2013
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Identification of myelosuppressive cytokines taking advantage of genomic abnormalities of leukocytes in patients with aplastic anemia
利用再生障碍性贫血患者白细胞基因组异常鉴定骨髓抑制细胞因子
- 批准号:
24390243 - 财政年份:2012
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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 - 财政年份:2011
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
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 - 财政年份:2009
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of novel auto-antibodies and corresponding antigens in patients with aplastic anemia using CLIP replacement Ii chain library
使用CLIP替换Ii链文库鉴定再生障碍性贫血患者的新型自身抗体和相应抗原
- 批准号:
19390260 - 财政年份:2007
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of autoantigens in aplastic anemia : identification of an epitope recognized by CD4^+ T cells specific to hematopoietic progenitor cells
再生障碍性贫血中自身抗原的分析:鉴定造血祖细胞特异的 CD4^ T 细胞识别的表位
- 批准号:
15390298 - 财政年份:2003
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of autoantigens in immune-mediated aplastic anemia-identification of an epitope of a CD4^+ T-cell clone
免疫介导的再生障碍性贫血中自身抗原的分析-CD4+T细胞克隆表位的鉴定
- 批准号:
13470202 - 财政年份:2001
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of autoantigens in autoimmune aplastic anemia
自身免疫性再生障碍性贫血中自身抗原的鉴定
- 批准号:
11670987 - 财政年份:1999
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of heat shock protein 70 as a causal molecule of aplastic anemia
再生障碍性贫血致病分子热休克蛋白 70 的分析
- 批准号:
09671103 - 财政年份:1997
- 资助金额:
$ 9.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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