Establishment of diagnosis and stem cell transplantation therapy regarding severe combined immunodeficiency

严重联合免疫缺陷诊断及干细胞移植治疗的建立

基本信息

批准号：
17591078
负责人：
AGEMATSU Kazunaga
金额：
$ 2.18万
依托单位：
SHINSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

项目摘要

Patients with severe combined immunodeficiency (SCID) is a disorder of poor prognosis. A subgroup of SCID increased cellular radiation sensitivity (RS-SCID) have mutations of Artemis, a gene that encodes a protein essential for V(D)J recombination and DNA double-strand break repair. We have identified three Japanese boys and one girl from four unrelated families with RS-SCID caused by a genomic exon 3 deletion of the Artemis gene, resulting in loss of exon 3 and skipping of exon 4. Two patients were homozygous and two patients were heterozygous for this novel mutation. Those parents studied were heterozygous for this mutation. Although two infants underwent successful bone marrow transplantation and immune reconstitution, the long-term outcome of this procedure is uncertain, because Artemis is expressed in most tissues and lack of its function in cells other than those derived from hematopoietic stem cells may increase the risk of malignancies.A diagnosis tends to be late, and because transplantation methods are not unified, the treatment of SCID is different the hospital. We are able to establish a genetic analysis in Japan, and develop early diagnosis and hematopoietic stem cell transplantation methods of severe combined immunodeficiency by this study. In these two years, we were able to make transplantation protocol of severe combined immunodeficiency jointly. In addition, we] could do presentation of severe combined immunodeficiency and other immunodeficiency.

严重合并免疫缺陷（SCID）的患者是预后不良的疾病。 SCID的亚组增加了细胞辐射敏感性（RS-SCID）具有Artemis的突变，Artemis是一种编码V（d）J重组和DNA双链破裂修复必不可少的蛋白质的基因。我们已经确定了来自四个无关家族的三个日本男孩和一名女孩，这是由基因组外显子3缺失引起的，导致Artemis基因缺失，导致外显子3和外显子4的跳过。两名患者是纯合子，两名患者是这项小说突变的杂合子。那些研究的父母是这种突变的杂合。尽管两个婴儿接受了成功的骨髓移植和免疫重构，但该程序的长期结局尚不确定，因为大多数组织中的Artemis表达了ARTEMIS，并且在细胞中缺乏其功能，而不是造血干细胞以外的细胞功能，可能会增加恶性肿瘤的风险。诊断趋向于较晚，并且由于无法进行治疗，因此无法单位进行治疗。我们能够在日本建立遗传分析，并通过这项研究发展早期诊断和造血干细胞移植方法。在这两年中，我们能够共同制定严重合并免疫缺陷的移植方案。此外，我们可以表明严重的免疫缺陷和其他免疫缺陷。