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Analysis of the novel gene identified using a SEREX method in the senrm of bone marrow failure patients

骨髓衰竭患者血清中SEREX方法鉴定的新基因分析

基本信息

批准号：
18591048
负责人：
FURUKAWA Tatsuo
金额：
$ 2.49万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591048/
关键词：
SEREX Bone Marrow Failure Zinc Finger Motif ZNF292 Leukemia cell line Zinc Finger motif

项目摘要

To identify novel autoantibodies in acquired aplastic anemia (AA), we screened the sera of patients with AA for the presence of antibodies (Abs) which recognize proteins derived from a normal bone marrow mononuclear cells. Immunoblotting using SEREX method revealed the presence of IgG Abs specific to ZNF292 (also known as IUAA0530, Zn-16) protein. This gene maps on chromosome 6, at 6q15 and contains 8 exons. Complete mRNA is 10610bp long. Northern blot analysis revealed that the gene strongly express in placenta, testis, prostate and thyroid gland, and weak expression is detected in heart, brain, spleen, thymus, adrenal gland, skeletal musde and peripheral lymphocytes. This gene encodes a protein which contains 7 zinc finger, C2H2-type domains. The protein binds to an evolutionarily conserved sequence in the growth hormone gene required for effective Pit-1-dependent activation of this promoter in vivo. The antibody recognized region contained zinc finger motifs which were recognized for the binding for promoter of GH gene. In 7 of 25 AA patients, an immunoglobulin G (IgG) antibody response was detected to ZNF292 gene. Intriguingly, antibody response was detected in 5 out of 9 AA patients with HLA DRB1*1501, and in only 1 out of 11 AA patients without HLA DRB1*1501. We also tried to identify the peptide sequences to activate CD8+ cytotoxic T cells(CIL). We could identify the surrogate peptides which supposed to bind HLA A2402, but we failed to identify the real peptide which had a potential to activate CILs.

为了鉴定获得性再生障碍性贫血（AA）中的新型自身抗体，我们筛选了AA患者血清中存在的识别来自正常骨髓单核细胞的蛋白质的抗体（Abs）。使用SEREX方法的免疫印迹显示存在ZNF 292（也称为IUAA 0530，Zn-16）蛋白的特异性IgG Ab。该基因定位于6号染色体6 q15，包含8个外显子。全长10610 bp。北方杂交结果显示，该基因在胎盘、睾丸、前列腺和甲状腺中有强表达，在心、脑、脾、胸腺、肾上腺、骨骼肌和外周血淋巴细胞中有弱表达。该基因编码的蛋白质含有7个锌指结构域，C2 H2型结构域。该蛋白质结合到生长激素基因中的进化上保守的序列，该序列是该启动子在体内有效的Pit-1依赖性激活所必需的。抗体识别区含有锌指基序，可与GH基因启动子结合。在25例AA患者中，7例检测到ZNF 292基因的IgG抗体应答。有趣的是，在9名具有HLA-DRB 1 *1501的AA患者中有5名检测到抗体应答，而在11名不具有HLA-DRB 1 *1501的AA患者中仅1名检测到抗体应答。我们还试图鉴定激活CD 8+细胞毒性T细胞（CIL）的肽序列。我们可以鉴定出与HLA A2402结合的替代肽，但我们未能鉴定出具有激活CIL潜力的真实的肽。