Molecular immunological analysis of the pathogenesis of Wiskott Aldrich syndrome associated IgA nephropathy

Wiskott Aldrich综合征相关IgA肾病发病机制的分子免疫学分析

• 批准号: 21790972
• 负责人: SHIMIZU Masaki
• 金额: $ 2.66万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790972/
• 关键词: Wiskott-Aldrich症候群; IgA腎症; 糖鎖不全

We evaluated the role of aberrant IgA production in the development of autoimmunity and glomerulonephritis in 26 patients with WAS. We found that serum galactose-deficient IgA levels and the levels of CIC containing IgA and IgG increased in WAS patients as an age dependent manner. Interestingly, these levels significantly increased in WAS patients with autoimmune manifestations. Furthermore, IgA-dominant immune deposits in the renal mesangium and glomerular injury in an XLT patient were significantly reduced after BMT. Galactose-deficient IgA levels were also markedly decreased after BMT. These findings indicate that mutations in WAS may be associated with aberrant IgA production and the development of autoimmune diseases including IgAN. Furthermore, immune reconstitution by BMT could correct aberrant IgA induced autoimmune diseases. These findings indicate that aberrant IgA production due to mutations in the WAS gene may be critically involved in the development of autoimmune diseases and glomerulonephritis.

我们在26例WAS患者中评估了异常IgA产生在自身免疫和肾小球肾炎发展中的作用。我们发现血清半乳糖缺乏IgA水平和含有IgA和IgG的CIC水平在WAS患者中呈年龄依赖性增加。有趣的是，这些水平在有自身免疫表现的WAS患者中显著升高。此外，在肾系膜和肾小球损伤的XLT患者中，iga显性免疫沉积在BMT后显著减少。半乳糖缺乏IgA水平在BMT后也显著降低。这些发现表明WAS的突变可能与异常的IgA产生和包括IgAN在内的自身免疫性疾病的发展有关。此外，BMT的免疫重建可以纠正异常IgA诱导的自身免疫性疾病。这些发现表明，由于WAS基因突变引起的异常IgA产生可能在自身免疫性疾病和肾小球肾炎的发展中起关键作用。

项目成果

Increased aberrant IgA production and development of immune-complex mediated glomerulonephritis in wiskott-aldrich syndrome protein deficiency

威斯科特-奥尔德里奇综合征蛋白质缺乏症中异常 IgA 产生增加和免疫复合物介导的肾小球肾炎的发展

• 发表时间: 2010
• 作者: 清水正樹,金兼弘和,元吉八重子,森尾友宏;Fabio Candotti,谷内江昭宏;Shimizu M.
• 通讯作者: Shimizu M.

WASP欠損によるIgA糖鎖不全と糸球体腎炎に関する解析

WASP缺陷导致的IgA糖链不足与肾小球肾炎分析

• 发表时间: 2010
• 作者: 清水正樹,金兼弘和,元吉八重子,森尾友宏;Fabio Candotti,谷内江昭宏;Shimizu M.;清水正樹
• 通讯作者: 清水正樹

Wiskott-Aldrich症候群におけるIgA糖鎖不全と免疫複合体形成

Wiskott-Aldrich 综合征中 IgA 糖基化缺陷和免疫复合物形成

• 发表时间: 2012
• 作者: 清水正樹,金兼弘和,元吉八重子,森尾友宏;Fabio Candotti,谷内江昭宏
• 通讯作者: Fabio Candotti,谷内江昭宏