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Development of molecular biological methods for diagnosis and treatment of severe combined immunodeficiency

严重联合免疫缺陷诊断和治疗的分子生物学方法的发展

基本信息

批准号：
06670783
负责人：
TSUGE Ikuya
金额：
$ 1.34万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670783/
关键词：
Severe Combined Immunodeficiency mutation analysis 遺伝子診断法遺伝子治療法

项目摘要

Severe combined immunodeficiency (SCID) is an inherited immunodeficiency disease in man, characterized by profound abnormalities of both the cellular and humoral arms of the immune system. Among the classic types of SCID,SCID with a normal number of BETA lymphocytes usually demonstrates an CHI-linked inheritance and now is regarded as common gamma-chain gene defect. Here, we report the characterization of mutations in the common gamma-chain gene of eight unrelated SCID with BETA cells patients. One large deletion, one short deletion, one nonsense mutation and four single missense mutations were identified. Three missense mutations were located near the motifs common to members of the class IOTA cytokine receptor family and a methionine at the beginning of the translation was mutated in remaining one patient.Of these eight patients, five received bone marrow transplantation (BMT). Although three patients developed full TAU-and BETA-cell response after HLA-genotypically identical BMT,antibody response remain absent in two patients who received HLA-partially phenotypically identical BMT.In both cases, patient derived BETA cells remain for a long period. As EB-virus transformed BETA cells from patients produce immunoglobulins in vitro, BETA cells in patients might be in an anagy-like state. The exact mechanism of antibody deficiency after BMT remained to be determined.

严重联合免疫缺陷(SCID)是一种遗传性免疫缺陷疾病，其特征是免疫系统的细胞和体液臂严重异常。在SCID的经典类型中，β淋巴细胞数量正常的SCID通常表现为CHI连锁遗传，目前被认为是常见的伽马链基因缺陷。在这里，我们报告了8名与β细胞无关的SCID患者常见伽马链基因突变的特征。鉴定出1个大缺失、1个短缺失、1个无义突变和4个单个错义突变。3个错义突变位于类细胞因子受体家族成员共同的基序附近，其余1名患者在翻译开始时发生蛋氨酸突变。在这8名患者中，5名接受了骨髓移植(BMT)。虽然3名患者在接受了人类白细胞抗原表型完全相同的骨髓移植后出现了完全的TAU和β细胞反应，但在接受了人类白细胞抗原部分表型完全相同的骨髓移植的患者中，两名患者仍然没有抗体反应。在这两种情况下，患者来源的β细胞保留了很长一段时间。由于EB病毒转化的患者β细胞在体外产生免疫球蛋白，患者的β细胞可能处于类衰老状态。骨髓移植后抗体缺失的确切机制尚不清楚。