Pathogenetic mechanisms of autoimmune pancreatitis and sclerosing cholangitis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590810
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kansai Medical University
• Principal Investigator: OKAZAKI Kazuichi Kansai Medical University, 医学部, 教授 (70145126)
• Co-Investigator(Kenkyū-buntansha): MATSUZAKI Koichi 関西医科大学, 医学部, 准教授 (70278638) ; UCHIDA Kazushige 関西医科大学, 医学部, 講師 (40411516)
• Project Period (FY): 2008 – 2010
• Keywords: 自己免疫性膵炎 / IgG4 / 硬化性胆管炎 / 動物モデル

Research Abstract

Our study clarified that the patients with IgG4-related autoimmune pancreatitis (AIP), and sclerosing cholangitis (SC) and animal experimental models showed autoimmune responses against carbonic anhydrase II (CA-II), lactoferrin and pancreatic secretory trypsin inhibitor (PSTI). Both Th1 and Th2, but not Th17 immune cells are involved in the development of these lesions. Moreover, regulatory T cells (Tregs), especially ICOS+Tregs are involved in IgG4 production in patients with IgG4-related AIP and SC.

Research Products

• [Journal Article] Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis. (2011)
  • Author(s): Tomiyama T, Uchida K, Matsushita M, Ikeura T, Fukui T, Takaoka M, Nishio A, Okazaki K.
  • Journal Title: J Gastroenterol. 46 Pages: 696-704
  • Peer Reviewed
• [Journal Article] Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. (2011)
  • Author(s): Okazaki K, Uchida K, Koyabu M, Miyoshi H, Takaoka M
  • Journal Title: J Gastroenterol. 46(3) Pages: 277-88
  • Peer Reviewed
• [Journal Article] The Role of Innate Immunity in the Pathogenesis of Experimental Autoimmune Pancreatitis in Mice. (2011)
  • Author(s): Nishio A, Asada M, Uchida K, Fukui T, Chiba T, Okazaki K
  • Journal Title: Pancreas. Pancreas. 40(1) Pages: 95-102
  • Peer Reviewed
• [Journal Article] Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis : an international multicentre study. (2011)
  • Author(s): Sugumar A, Levy MJ, Kamisawa T, J M Webster G, Kim MH, Enders F, Amin Z, Baron TH, Chapman MH, Church NI, Clain JE, Egawa N, Johnson GJ, Okazaki K, Pearson RK, Pereira SP, Petersen BT, Read S, Sah RP, Sandanayake NS, Takahashi N, Topazian MD, Uchida K, Vege SS, Chari ST
  • Journal Title: Gut. 60(5) Pages: 666-70
  • Peer Reviewed
• [Journal Article] Analysis of humoral immune response in experimental autoimmune pancreatitis in mice. (2010)
  • Author(s): Asada M, Nishio A, Akamatsu T, Tanaka J, Saga K, Kido M, Watanabe N, Uchida K, Fukui T, Okazaki K, Chiba T
  • Journal Title: Pancreas. 39(2) Pages: 224-31
  • Peer Reviewed
• [Journal Article] Primary sclerosing cholangitis with elevated serum IgG4 levels and/or infiltration of abundant IgG4-positive plasma cells. (2010)
  • Author(s): Koyabu M, Uchida K, Fukata N, Kusuda T, Ikeura T, Sakaguchi Y, Yoshida K, Shimatani M, Fukui T, Matsushita M, Uemura Y, Kaibori M, Takaoka M, Nishio A, Okazaki K
  • Journal Title: J Gastroenterol. 45(1) Pages: 122-9
  • Peer Reviewed
• [Journal Article] Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. (2010)
  • Author(s): Koyabu M, Uchida K, Miyoshi H, Sakaguchi Y, Fukui T, Ikeda H, Takaoka M, Hirohara J, Nishio A, Uemura Y, Uemoto S, Okazaki K
  • Journal Title: J Gastroenterol. 45(7) Pages: 732-41
  • Peer Reviewed
• [Journal Article] Research Committee for Intractable Pancreatic Disease and Japan Pancreas Society. Japanese consensus guidelines for management of autoimmune pancreatitis : I. Concept and diagnosis of autoimmune pancreatitis. (2010)
  • Author(s): Okazaki K, Kawa S, Kamisawa T, Shimosegawa T, Tanaka M
  • Journal Title: J Gastroenterol. 45(3) Pages: 249-65
  • Peer Reviewed
• [Journal Article] Working members of Research Committee for Intractable Pancreatic Disease and Japan Pancreas Society. Japanese consensus guidelines for management of autoimmune pancreatitis : II. Extrapancreatic lesions, differential diagnosis. (2010)
  • Author(s): Kawa S, Okazaki K, Kamisawa T, Shimosegawa T, Tanaka M
  • Journal Title: J Gastroenterol. 45(4) Pages: 355-69
  • Peer Reviewed
• [Journal Article] Effective endoscope for endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anastomosis : a single-, double-, or "short" double-balloon enteroscope? (2010)
  • Author(s): Matsushita M, Shimatani M, Takaoka M, Okazaki K
  • Journal Title: Dig Dis Sci. 55(3) Pages: 874-5
  • Peer Reviewed
• [Journal Article] Research Committee for Intractable Pancreatic Disease and Japan Pancreas Society. Japanese consensus guidelines for management of autoimmune pancreatitis : III. Treatment and prognosis of AIP. (2010)
  • Author(s): Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M
  • Journal Title: J Gastroenterol. 45(5) Pages: 471-7
  • Peer Reviewed
• [Journal Article] Histopathologic and clinical subtypes of autoimmune pancreatitis : the Honolulu consensus document. (2010)
  • Author(s): Chari ST, Kloeppel G, Zhang L, Notohara K, Lerch MM, Shimosegawa T; Okazaki K, et al
  • Journal Title: Pancreas. 39(5) Pages: 549-54
  • Peer Reviewed
• [Journal Article] Autoimmune pancreatitis- a new evolving pancreatic disease? (2010)
  • Author(s): Okazaki K, Uchida K, Fukui T, Takaoka M, Nishio A
  • Journal Title: Langenbecks Arch Surg. 395(8) Pages: 989-1000
  • Peer Reviewed
• [Journal Article] Idiopathic duct-centric pancreatitis (IDCP) with immunological studies. (2010)
  • Author(s): Kusuda T, Uchida K, Satoi S, Koyabu M, Fukata N, Miyoshi H, Ikeura T, Sakaguchi Y, Yoshida K, Fukui T, Shimatani M, Matsushita M, Takaoka M, Nishio A, Uemura Y, Kwon AH, Okazaki K
  • Journal Title: Intern Med. 49(23) Pages: 2569-75
  • Peer Reviewed
• [Journal Article] Recent Concepts of Autoimmune Pancreatitis and IgG4-Related Disease. (2010)
  • Author(s): Okazaki K, Uchida K, Miyoshi H, Ikeura T, Takaoka M, Nishio A
  • Journal Title: Clin Rev Allergy Immunol. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Long-term outcome of autoimmune pancreatitis. (2009)
  • Author(s): Uchida K, Yazumi S, Nishio A, Kusuda T, Koyabu M, Fukata M, Miyoshi H, Sakaguchi Y, Fukui T, Matsushita M, Takaoka M, Okazaki K
  • Journal Title: J Gastroenterol. 44(7) Pages: 726-32
  • Peer Reviewed
• [Journal Article] Standard steroid therapy for autoimmune pancreatitis. (2009)
  • Author(s): Kamisawa T, Shimosegawa T, Okazaki K, Nishino T, Watanabe H, Kanno A, Okumura F, Nishikawa T, Kobayashi K, Ichiya T, Takatori H, Yamakita K, Kubota K, Hamano H, Okamura K, Hirano K, Ito T, Ko S, Omata M
  • Journal Title: Gut. 58(11) Pages: 1504-7
  • Peer Reviewed
• [Journal Article] Atypical retroperitoneal fibrosis associated with biliary stricture : IgG4-related sclerosing disease? (2009)
  • Author(s): Matsushita M, Fukui T, Uchida K, Nishio A, Okazaki K
  • Journal Title: Scand J Gastroenterol. 44(9) Pages: 1146-7
  • Peer Reviewed
• [Journal Article] Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice. (2009)
  • Author(s): Yoshida K, Yang GX, Zhang W, Tsuda M, Tsuneyama K, Moritoki Y, Ansari AA, Okazaki K
  • Journal Title: Hepatology. 50(5) Pages: 1494-500
  • Peer Reviewed
• [Journal Article] Japanese clinical guidelines for autoimmune pancreatitis. (2009)
  • Author(s): Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H, Irisawa A, Kubo K, Notohara K, Hasebe O, Fujinaga Y, Ohara H, Tanaka S, Nishino T, Nishimori I, Nishiyama T, Suda K, Shiratori K, Shimosegawa T, Tanaka M
  • Journal Title: Pancreas. 38(8) Pages: 849-66
  • Peer Reviewed
• [Presentation] Autoimmune Pancreatitis-recent concept and the Japanese experience. (2010)
  • Author(s): 岡崎和一
  • Organizer: Annual meeting of Gastroenterological Association of Thailand. Pattaya.
  • Year and Date: 2010-11-17
• [Presentation] Analysis of ICOS and IL-10 positive regulatory T cells in patients with autoimmune pancreatitis. (2010)
  • Author(s): K Uchida, T Kusuda, K Okazaki, et al
  • Organizer: American Pancreatic Association Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2010-11-06
• [Presentation] 自験例よりみた自己免疫性膵炎の治療法とその予後 (2010)
  • Author(s): 内田一茂、岡崎和一
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-12
• [Presentation] 自己免疫性膵炎をめぐる新たな展開自己免疫性膵炎(AIP-LPSP)と好中球病変(IDCP)の免疫学的相違に関する検討 (2010)
  • Author(s): 楠田武生,内田一茂,岡崎和一
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-10-12
• [Presentation] Relationship between T cells and IgG4-positive plasma cells in the involved. (2010)
  • Author(s): K.Uchida, M.Koyabu, T.Kusuda, H.K.Okazaki, et al.
  • Organizer: International congress of Immunology 2010
  • Place of Presentation: Kobe
  • Year and Date: 2010-10-08
• [Presentation] Involvement of ICOS and IL-10 positive regulatory T cells in the development of autoimmune pancreatitis. (2010)
  • Author(s): Kazushige Uchida, Takeo Kusuda, Masanori Koyabu, Kazuichi Okazaki, et al
  • Organizer: Joint meeting of the International Association of Pancreatology and the Japan Pancreas Society
  • Place of Presentation: Fukuoka
  • Year and Date: 2010-07-01
• [Presentation] Possible role of regulatory T cells in producing IgG4 in the involved organs with autoimmune pancreatitis. (2010)
  • Author(s): Koyabu M, Uchida K, Okazaki K, et al
  • Organizer: DDW2010.
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-06
• [Presentation] 自己免疫性膵炎における制御性T細胞に関する検討 (2009)
  • Author(s): 内田一茂,楠田武生、岡崎和一
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-12
• [Presentation] Analysis of Regulatory T cells in Patients with Autoimmune pancreatitis. (2009)
  • Author(s): Uchid K, Miyosi H, Okazkai K, et al
  • Organizer: 40th Anniversary Meeting of American Pancreatic Association and Japan Pancreatic Society.
  • Place of Presentation: Honolulu
  • Year and Date: 2009-11-05
• [Presentation] An animal model for acute, chronic, and severe pancreatitis with the analyses of regeneration mechanismas. (2009)
  • Author(s): Y Sakaguchi, T Kusuda, M K Okazaki
  • Organizer: 40th Anniversary Meeting of American Pancreatic Association (APA) and Japan Pancreatic Society (JPS).
  • Place of Presentation: Honolulu
  • Year and Date: 2009-11-05
• [Presentation] How Do We Diagnose AIP? (2009)
  • Author(s): 岡崎和一
  • Organizer: 40th Anniversary Meeting of APA and JPS.
  • Place of Presentation: Honolulu
  • Year and Date: 2009-11-05
• [Presentation] Subtypes of AIP (LPSP AND IDCP). (2009)
  • Author(s): 岡崎和一
  • Organizer: 40th Anniversary Meeting of APA and JPS.
  • Place of Presentation: Honolulu
  • Year and Date: 2009-11-05
• [Presentation] Regulatory T cells in patients with autoimmune pancreatitis. (2009)
  • Author(s): Uchida K, Miyoshi H, Okazaki K, et al
  • Organizer: European Pancreatic Club Meeting
  • Place of Presentation: Szeged, Hungary
  • Year and Date: 2009-10-01
• [Presentation] 自己免疫性膵炎における制御性T細胞とIgG4に関する検討 (2009)
  • Author(s): 内田一茂、小薮雅紀、楠田武夫、三好秀明、坂口雄沢、西尾彰功、岡崎和一
  • Organizer: 日本消化器免疫学会
  • Place of Presentation: 松山
  • Year and Date: 2009-09-10
• [Presentation] ANATOMY of a FRIENDSHIP Gunter Kloppel & the Verona Pancreatic Team (2009)
  • Author(s): 岡崎和一
  • Place of Presentation: Verona
  • Year and Date: 2009-09-09
• [Presentation] Analysis of CD4+CD25high regulatory T cells in patients with autoimmune pancreatitis. (2009)
  • Author(s): Uchida K, Miyoshi H, Okazaki K, et al
  • Organizer: International Pancreatic Research Forum
  • Place of Presentation: Tokyo
  • Year and Date: 2009-01-12
• [Book] 見て診て学ぶ膵腫瘍の画像診断 (2009)
  • Author(s): 岡崎和一、内田一茂、福井寿朗
  • Total Pages: 391
  • Publisher: 永井書店
• [Book] 新版自己免疫性膵炎-病態から診断・治療まで- (2009)
  • Author(s): 岡崎和一、川茂幸、神澤輝実
  • Total Pages: 216
  • Publisher: 診断と治療社