A immunological study of target antigens in patients with autoimmune pancreatitis and animal models

自身免疫性胰腺炎患者靶抗原及动物模型的免疫学研究

• 批准号: 16590645
• 负责人: OKAZAKI Kazuichi
• 金额: $ 2.18万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590645/
• 关键词: autoimmune pancreatitis; carbonic anhydrase; lactoferrin; PSTI; Th1; Th2 balance

Background and aim : Although an autoimmune mechanism may be involved in autoimmune pancreatitis (AIP), the pathogenesis still remains unclear. We previously reported that autoantibodies against carbonic anhydrase II (CA-II) and lactoferrin (LF) are frequently observed in AIP patients. However, approximately 10 % of patients with AIP show negative antibodies against CA-II or LF. The aim of this study is to find novel autoantibodies in AIP. Subjects : Twenty-six patients with AIP, 10 patients with alcoholic chronic pancreatitis, 10 patients with idiopathic chronic pancreatitis, 17 patients with acute pancreatitis, 16 patients with pancreatic cancer, and 12 normal subjects as control were recruited for the study. Methods : We performed the immuno-screening using human pancreatic cDNA library and patients' sera. Positive clones were analyzed by DNA sequencing, and constructed into the expression vector pGEX-4T-1. The recombinant proteins were expressed as glutathione S-transferase fusion protein in E.coli. The serum levels of the newly identified autoantibody were measured by enzyme linked immunosorbent assay. Results : We cloned a cDNA encoding entire coding sequence of the human pancreatic secretory trypsin inhibitor (PSTI) cDNA by the immuno-screening. Serum levels of anti-human PSTI antibody were increased in 30.8% (8/26) of AIP patients in comparison with those in alcoholic chronic pancreatitis, idiopathic chronic pancreatitis, acute pancreatitis, pancreatic cancer, and in normal subjects. Conclusions : Anti-human PSTI antibody, a novel autoantibody with AIP, may be involved in the pathophysiology and useful as a diagnostic marker in patients with AIP.

背景与目的：尽管自身免疫性胰腺炎（AIP）可能涉及自身免疫机制，但其发病机制仍不清楚。我们之前报道过，在 AIP 患者中经常观察到针对碳酸酐酶 II (CA-II) 和乳铁蛋白 (LF) 的自身抗体。然而，大约 10% 的 AIP 患者显示针对 CA-II 或 LF 的阴性抗体。本研究的目的是寻找 AIP 中的新型自身抗体。受试者：26 名 AIP 患者、10 名酒精性慢性胰腺炎患者、10 名特发性慢性胰腺炎患者、17 名急性胰腺炎患者、16 名胰腺癌患者以及 12 名正常对照者纳入研究。方法：利用人胰腺cDNA文库和患者血清进行免疫筛选。对阳性克隆进行DNA测序分析，构建表达载体pGEX-4T-1。重组蛋白在大肠杆菌中表达为谷胱甘肽S-转移酶融合蛋白。通过酶联免疫吸附测定法测量新鉴定的自身抗体的血清水平。结果：通过免疫筛选，我们克隆了编码人胰腺分泌性胰蛋白酶抑制剂（PSTI）cDNA完整编码序列的cDNA。与酒精性慢性胰腺炎、特发性慢性胰腺炎、急性胰腺炎、胰腺癌和正常人相比，30.8%（8/26）的AIP患者血清抗人PSTI抗体水平升高。结论：抗人 PSTI 抗体是一种新型 AIP 自身抗体，可能参与 AIP 的病理生理学过程，可作为 AIP 患者的诊断标志物。

项目成果

Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas.

唾液腺多形性腺瘤中软骨特异性基质蛋白软骨调节素-I mRNA 的表达和定位。

• 发表时间: 2005
• 期刊: Vurcgiws Arch 446(1)
• 作者: Kusafuka K;Nakano K;Okazaki K;et al.
• 通讯作者: et al.

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis

• DOI: 10.1097/01.mpa.0000226881.48204.fd
• 发表时间: 2006-07-01
• 期刊: PANCREAS
• 影响因子: 2.9
• 作者: Asada, Masanori;Nishio, Akiyoshi;Okazaki, Kazuichi
• 通讯作者: Okazaki, Kazuichi

A case of autoimmune pancreatitis associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjogren's syndrome

• DOI: 10.1159/000084494
• 发表时间: 2005-01-01
• 期刊: PANCREATOLOGY
• 影响因子: 3.6
• 作者: Fukui, T;Okazaki, K;Chiba, T
• 通讯作者: Chiba, T

Association of HLA and autoantibodies against the exocrine pancreas in type 1 diabetes.

1 型糖尿病中 HLA 与抗外分泌胰腺自身抗体的关联。

• 发表时间: 2004
• 期刊: Pancreas 29(3)
• 作者: Taniguchi T;Okazaki K;et al.
• 通讯作者: et al.

Autoantibodies against the exocrine pancreas in fulminant type 1 diabetes.

暴发性 1 型糖尿病中针对外分泌胰腺的自身抗体。

• 发表时间: 2005
• 期刊: Pancreas 30(2)
• 作者: Tsukiyama K;Taniguchi T;Takehiro M;Miki T;Ueno H;Zhou H;Shimono D;Taniguchi T
• 通讯作者: Taniguchi T