Clarification of the etiopathogenesis of IgG4-related disease: Establishment of a mouse model based on abnormal T cell functional abnormalities

阐明IgG4相关疾病的发病机制：基于异常T细胞功能异常的小鼠模型的建立

• 批准号: 23591460
• 负责人: KAWANO Mitsuhiro
• 金额: $ 3.33万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591460/
• 关键词: IgG4関連疾患; モデルマウス; APRIL; Th2

We evaluated whether Lat Y136F knock-in mice, which show Th2 predominant immunoreaction with increased serum IgG1, a counterpart of human IgG4, are a novel mice model for IgG4-related disease (IgG4-RD). Lat Y136F knock-in mice showed a similar pathology to that of human IgG4-RD in kidney, pancreas and salivary glands, and a good response to corticosteroid. These results suggested that Lat Y136F knock-in mice are a novel mice model for IgG4-RD. Next, we analyzed the role of APRIL in IgG4-RD using Lat Y136F knock-in mice. We administered APRIL blocking antibody to Lat Y136F knock-in mice, and found that the inflammation in kidney in an APRIL blocking antibody group was significantly decreased as compared to that in a control group. This result indicated that APRIL plays some role in the promotion of lesions at least in IgG4-related kidney disease.

我们评估了 Lat Y136F 敲入小鼠是否是 IgG4 相关疾病 (IgG4-RD) 的新型小鼠模型，该小鼠表现出 Th2 主要免疫反应，血清 IgG1（人 IgG4 的对应物）增加。 Lat Y136F 敲入小鼠在肾脏、胰腺和唾液腺中表现出与人 IgG4-RD 相似的病理学，并且对皮质类固醇有良好的反应。这些结果表明 Lat Y136F 敲入小鼠是 IgG4-RD 的新型小鼠模型。接下来，我们使用 Lat Y136F 敲入小鼠分析了 APRIL 在 IgG4-RD 中的作用。我们给Lat Y136F敲入小鼠施用APRIL阻断抗体，发现APRIL阻断抗体组的肾脏炎症与对照组相比显着减轻。该结果表明，APRIL至少在IgG4相关的肾脏疾病中具有促进病变的作用。

项目成果

Analysis of pancreatic endocrine function in patients with IgG4-related diseases, in whom autoimmune pancreatitis was ruled out by diagnostic imaging.

IgG4相关疾病患者胰腺内分泌功能分析，通过影像诊断排除自身免疫性胰腺炎。

• 发表时间: 2014
• 期刊: Endocr J
• 影响因子: 2
• 作者: Ito N;Yagi K;Kawano M;Mori Y;Okazaki S;Chujo D;Takeda Y;Kobayashi J;Yamagishi M
• 通讯作者: Yamagishi M

Immunohistochemical Characteristics of IgG4-Related Tubulointerstitial Nephritis: Detailed Analysis of 20 Japanese Cases.

• DOI: 10.1155/2012/609795
• 发表时间: 2012
• 期刊: International journal of rheumatology
• 影响因子: 2.3
• 作者: Kawano M;Mizushima I;Yamaguchi Y;Imai N;Nakashima H;Nishi S;Hisano S;Yamanaka N;Yamamoto M;Takahashi H;Umehara H;Saito T;Saeki T
• 通讯作者: Saeki T

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease.

• DOI: 10.1155/2012/580814
• 发表时间: 2012
• 期刊: International journal of rheumatology
• 影响因子: 2.3
• 作者: Masaki Y;Kurose N;Yamamoto M;Takahashi H;Saeki T;Azumi A;Nakada S;Matsui S;Origuchi T;Nishiyama S;Yamada K;Kawano M;Hirabayashi A;Fujikawa K;Sugiura T;Horikoshi M;Umeda N;Minato H;Nakamura T;Iwao H;Nakajima A;Miki M;Sakai T;Sawaki T;Kawanami T;Fujita Y;Tanaka M;Fukushima T;Eguchi K;Sugai S;Umehara H
• 通讯作者: Umehara H

Prurigo nodularis-like skin eruptions in a patient with IgG4-related disease

IgG4 相关疾病患者出现结节性痒疹样皮疹

• DOI: 10.1684/ejd.2013.2077
• 发表时间: 2013
• 期刊: Eur J Dermatol
• 影响因子: 2.5
• 作者: Hamaguchi Y;Yamada K;Kawano M;Fujimoto M;Takehara K
• 通讯作者: Takehara K

Overview of New Entities within the IgG4-RD spectrum

IgG4-RD 谱中的新实体概述

• 发表时间: 2014
• 作者: Kazunori Yamada;Takahiro Kawakami;Ichiro Mizushima;Ryoko Hamano;Hiroshi Fujii;Masakazu Yamagishi;and Mitsuhiro Kawano;Mitsuhiro Kawano
• 通讯作者: Mitsuhiro Kawano