Immunological study of autoimmune pancreatitis

自身免疫性胰腺炎的免疫学研究

• 批准号: 11670495
• 负责人: OKAZAKI Kazuichi
• 金额: $ 2.5万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670495/
• 关键词: autoimmune; pancreatitis

We observed that several autoantibodies such as antinuclear antibody (ANA), anti-lactoferrin (LF) antibody (ALF), anti-carbonic anhydrase-II (CA-II) antibody (ACA-II ), rheumatoid factor and antismooth muscle antibody were frequently detected in patients with. The high prevalence of these antibodies suggests that CA-II and LF may be the candidates for the target antigens in AIP.Although the effector cells of AIP have been poorly understood, the activated CD4+ and CD8+ T-cells bearing HLA-DR and CD45RO were increased in the peripheral blood lymphocytes (PBLs) in the patients with AIP in comparison with those in other causes of pancreatitis such as alcoholic or gallstone-related pancreatitis. CD4+ T-cells also predominantly infiltrate in the pancreas tissue over CD8+ T-cells. Similar to SjS or PSC, CD4+ T-cells showing Th1 type of immune response are predominantly involved in the development of AIP as effector cells over Th2 type CD4+ T-cells. In some patients with AIP, HLA-DR antigens a … More re expressed on the pancreatic duct cells as well as CD4+ T-cells. Neonatally thymectomized (nTx) mice subcutaneally immunized with CA-II or LF, and synergetic nude mice, transferred with seplenocytes from the disease-induced nTx-mice, developed pancreatitis as well as sialoadenitis and cholangitis, but the normal BALA/c mice did not. In our animal model using nTx-BALB/c mice and transferred nude mice, the CD4-positive cells were mainly involved in the development of pancreatitis, sialoadenitis and cholangitis, while CD8+ T-cells were never pathogenic. These findings suggested that MHC-class II restricted-autoreactive CD4+T-cells, which escape from the negative selection in the thymus, and depletion of regulatory T-cells such as CD25+ T-cells in the periphery take important roles in the development of autoimmune pancreatitis and exocrinopathy. These animal models suggest that although CD8+ T-cells may be partially involved, CD4+ T-cells take major roles in the development of experimental pancreatitis, which is consistent with human AIP. Less

我们观察到，抗核抗体（ANA）、抗乳铁蛋白（LF）抗体（ALF）、抗碳酸酐酶-II（CA-II）抗体（ACA-II）、类风湿因子和抗平滑肌抗体等多种自身抗体在患者中频繁检出。这些抗体的高流行率表明CA-II和LF可能是AIP靶抗原的候选者。尽管对AIP的效应细胞了解甚少，但与其他原因引起的AIP患者相比，AIP患者外周血淋巴细胞（PBL）中携带HLA-DR和CD45RO的活化CD4+和CD8+ T细胞增多。 胰腺炎，例如酒精性或胆结石相关性胰腺炎。 CD4+ T 细胞也比 CD8+ T 细胞主要浸润胰腺组织。与 SjS 或 PSC 类似，显示 Th1 型免疫反应的 CD4+ T 细胞作为效应细胞（相对于 Th2 型 CD4+ T 细胞）主要参与 AIP 的发育。在一些 AIP 患者中，HLA-DR 抗原在胰管细胞和 CD4+ T 细胞上重新表达。用 CA-II 或 LF 皮下免疫的新生胸腺切除 (nTx) 小鼠，以及用来自疾病诱导的 nTx 小鼠的脾细胞移植的协同裸鼠，出现胰腺炎以及唾液腺炎和胆管炎，但正常 BALA/c 小鼠则没有。在我们使用 nTx-BALB/c 小鼠和移植裸鼠的动物模型中，CD4 阳性细胞主要参与胰腺炎、唾液腺炎和胆管炎的发展，而 CD8+ T 细胞从不致病。这些发现表明，MHC II 类限制性自身反应性 CD4+T 细胞（逃避胸腺的阴性选择）和外周调节性 T 细胞（如 CD25+T 细胞）的耗竭在自身免疫性胰腺炎和外分泌病的发展中发挥着重要作用。这些动物模型表明，尽管 CD8+ T 细胞可能部分参与其中，但 CD4+ T 细胞在实验性胰腺炎的发展中发挥着主要作用，这与人类 AIP 一致。较少的

项目成果

Adachi E,Okazaki K et al: "Acute pancreatitis secondary to 5-aminosali-cylic acid therapy in a patientswith ulceratiye coliti"Int J Pancreatol. 25. 219-223 (1999)

Adachi E、Okazaki K 等人：“溃疡性结肠炎患者继发于 5-氨基水杨酸治疗的急性胰腺炎”Int J Pancreatol。

Gastric aberrant pancreas: "endoscopic ultrasonographic analysis in comparison with the histology."Gastrointest Endosc. 49. 493-497 (1999)

胃异常胰腺：“内镜超声分析与组织学比较。”Gastrointest Endosc。

Nakamoto Y,OkazakiK: "Autoimmune pancreatitis with F-18fluoro-2-D-glucose PET findings."Clinical N,,clear Medicine. 24. 778-780 (1999)

Nakamoto Y，OkazakiK：“自身免疫性胰腺炎与 F-18 氟-2-D-葡萄糖 PET 结果。”临床 N，明确医学。

Kazuichi Okazaki, Kazushige Uchida, Masaya Ohana, Hiroshi Nakase, Suguru Uose, Maki Inal, Yumi Matsushima, Kenji Katamura, Katsuyuki Ohmori, Tsutomu Chiba: "Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2 type cellular immu

Kazuichi Okazaki、Kazushige Uchida、Masaya Ohana、Hiroshi Nakase、Suguru Uose、Maki Inal、Yumi Matsushima、Kenji Katamura、Katsuyuki Ohmori、Tsutomu Chiba：“自身免疫相关性胰腺炎与自身抗体和 Th1/Th2 型细胞免疫有关

Uchida K,Okazaki K: "Clinical evaluation of autoimmune-related pancreatitis."Am J Gastroenterol. 195. 2788-2794 (2000)

Uchida K、Okazaki K：“自身免疫相关胰腺炎的临床评估。”Am J Gastroenterol。