Study on the mechanism of autoimmunity and malignancy developed in primary immunodeficiency

原发性免疫缺陷自身免疫及恶性肿瘤发生机制的研究

• 批准号: 20591245
• 负责人: MORIO Tomohiro
• 金额: $ 2.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591245/
• 关键词: 先天性免疫不全症; 自己免疫疾患; 悪性腫瘍; DNA損傷修復; 毛細血管拡張小脳失調症; Mre11; V(D)J再構成; 免疫グロブリンクラススイッチ; ATM; リンパ系悪性腫瘍; 分類不能型免疫不全症; Mrel1欠損症; DNA損傷修復応答; ゲノム不安定性; T細胞サブセット; Anergy; B細胞新生能; T細胞新生能; Good症候群; DNA損傷修復異常

We studied on the mechanism of autoimmunity and malignancy frequently observed in patients with primary immunodeficiency (PID). Patients with impaired DNA damage response such as ataxia telangiectasia (AT) and Mre11 deficiency showed chromosomal abnormality caused by defect in DNA damage processing. AT patients showed defective T-cell development as well. T-cell anergy was not properly executed in lymphocytes from ICOS deficiency showing autoimmunity. Skewed TCR V repertoire usage was observed in ～50% of CVID patients. These findings suggest the presence of various mechanism underling autoimmune disorder and malignancy in PID patients.

对原发性免疫缺陷（PID）患者常见的自身免疫性疾病和恶性肿瘤的发生机制进行了研究。共济失调毛细血管扩张症（ataxia telangiectasia，AT）和Mre 11缺陷症等DNA损伤反应受损的患者表现为DNA损伤处理缺陷引起的染色体异常。AT患者也表现出T细胞发育缺陷。T细胞无反应性在显示自身免疫性的ICOS缺陷的淋巴细胞中没有正确执行。在约50%的CVID患者中观察到TCRV库使用偏斜。这些发现表明PID患者存在多种自身免疫性疾病和恶性肿瘤的机制。

项目成果

Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards

• DOI: 10.1016/j.jpeds.2009.05.026
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: Morinishi, Yoichi;Imai, Kohsuke;Nonoyama, Shigeaki
• 通讯作者: Nonoyama, Shigeaki

Immunologically silent cancer clone transmission from mother to offspring

• DOI: 10.1073/pnas.0904658106
• 发表时间: 2009-10-20
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Isoda, Takeshi;Ford, Anthony M.;Mizutani, Shuki
• 通讯作者: Mizutani, Shuki

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism

• DOI: 10.1007/s00431-009-1126-6
• 发表时间: 2010-07-01
• 期刊: EUROPEAN JOURNAL OF PEDIATRICS
• 影响因子: 3.6
• 作者: Inoue, Hirosuke;Takada, Hidetoshi;Hara, Toshiro
• 通讯作者: Hara, Toshiro

Analysis of mutations and recombination activity in RAG-deficient patient.

RAG 缺陷患者的突变和重组活性分析。

• 发表时间: 2011
• 期刊: Clin.Immunol
• 作者: Ozeki M;Kunishima S;Kasahara K;Funato M;Teramoto T;Kaneko H;Fukao T;Kondo N.;Asai E.Wada T.Sakakibara Y.Toga A.Toma T.Shimizu T.Imai K.Nonoyama S.Morio T.Kamachi Y.Ohara O.Yachie A.
• 通讯作者: Asai E.Wada T.Sakakibara Y.Toga A.Toma T.Shimizu T.Imai K.Nonoyama S.Morio T.Kamachi Y.Ohara O.Yachie A.

分類不能型免疫不全症診断の全国調査と亜群同定

全国不可分类免疫缺陷诊断和亚组识别调查

• 发表时间: 2010
• 作者: 森尾友宏;今井耕輔;小原収;金兼弘和;竹森利忠;田中敏郎;松本功;原寿郎
• 通讯作者: 原寿郎