Clinical and immunogenetic study for the association between autoimmune pancreatitis or IgG4-related disease and malignancy formation

• Project/Area Number: 15K09045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Matsumoto Dental University (2017); Shinshu University (2015-2016)
• Principal Investigator: Kawa Shigeyuki 松本歯科大学, 歯学部, 特任教授 (10177628)
• Co-Investigator(Kenkyū-buntansha): 太田 正穂 信州大学, 医学部, 特任教授 (50115333) ; 伊藤 哲也 信州大学, 医学部, 助教(特定雇用) (50748605) ; 亀子 文子 純真学園大学, 検査科学科, 教授 (60126670)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IgG4 / 自己免疫性膵炎 / IgG4関連疾患 / 悪性腫瘍 / 標準化罹患比 / IgG4関連動脈周囲病変 / 標準化死亡比 / 膵癌

Outline of Final Research Achievements

Because it is uncertain whether autoimmune pancreatitis (AIP) and immunoglobulin G4-related disease (IgG4-RD) are associated with malignancy, we evaluated the incidence of cancer development in a large cohort of patients with AIP and IgG4-RD. The overall standardized incidence ratio of malignancies for AIP and IgG4-RD were 2.08 (95% CI 1.32-2.85) and 2.01 (95% CI 1.34-2.69), respectively, which indicated a close association between both conditions and malignancy formation. The cumulative rate of malignancy development was significantly higher in patients with IgG4-RD within 12 years after diagnosis than in the Japanese general population.
We investigated immunogenetic backgrounds for AIP and IgG4-RD, and found that AIP has a close association with SNP other than rs3184504 which is functional SNP most prevalent in Japanese population, and the occurrence of IgG4-related periaortitis is cosely associated with IL1R1 polymorphism.

Research Products

• [Journal Article] IgG4-related Disease - A Systemic Disease that Deserves Attention Regardless of One's Subspecialty (2018)
  • Author(s): Hamano H, Tanaka E, Ishizaka N, Kawa S.
  • Journal Title: Internal Medicine Volume: 57 Issue: 9 Pages: 1201-1207
  • DOI: 10.2169/internalmedicine.9533-17
  • NAID: 130006730696
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Clinical course of type 1 autoimmune pancreatitis patients without steroid treatment: a Japanese multicenter study of 97 patients. (2018)
  • Author(s): Kubota K, Kamisawa T, Hirano K, Hirooka Y, Uchida K, Ikeura T, Shiomi H, Ohara H, Shimizu K, Arakura N, Kanno A, Sakagami J, Itoi T, Ito T, Ueki T, Nishino T, Inui K, Mizuno N, Yoshida H, Sugiyama M, Iwasaki E, Irisawa A, Okazaki K, Kawa S, Shimosegawa T, Takeyama Y, Chiba T.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 25 Issue: 4 Pages: 223-230
  • DOI: 10.1002/jhbp.541
  • Peer Reviewed
• [Journal Article] An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index. (2018)
  • Author(s): Wallace ZS, Khosroshahi A, Carruthers MD, Perugino CA, Choi H, Campochiaro C, Culver EL, Cortazar F, Della-Torre E, Ebbo M, Fernandes A, Frulloni L, Hart P, Karadag O, Kawa S, Kawano M, Kim MH, Lanzillotta M, Matsui S, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Tanasa P, Umehara H, Webster G, Zhang W, Stone JH.
  • Journal Title: Arthritis Care Res Volume: - Issue: 11 Pages: 1671-1678
  • DOI: 10.1002/acr.23543
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Promoter hypomethylation of SKI in autoimmune pancreatitis (2018)
  • Author(s): Kinugawa Y, Uehara T, Matsuda K, Kobayashi Y, Nakajima T, Hamano H, Kawa S, Higuchi K, Hosaka N, Shiozawa S, Ishigame H, Nakamura T, Maruyama Y, Nakazawa K, Nakaguro M, Sano K, Ota H.
  • Journal Title: Pathol Res Pract. Volume: 214 Issue: 4 Pages: 492-497
  • DOI: 10.1016/j.prp.2018.03.005
  • Peer Reviewed
• [Journal Article] Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis (2017)
  • Author(s): Kinugawa Y, Uehara T, Sano K, Matsuda K, Maruyama Y, Kobayashi Y, Nakajima T, Hamano H, Kawa S, Higuchi K, Hosaka N, Shiozawa S, Ishigame H, Ota H.
  • Journal Title: pancreas Volume: 46 Issue: 5 Pages: 614-618
  • DOI: 10.1097/mpa.0000000000000804
  • Peer Reviewed
• [Journal Article] Usefulness of three-dimensional magnetic resonance cholangiopancreatography with partial maximum intensity projection for diagnosing autoimmune pancreatitis. (2017)
  • Author(s): Yanagisawa S, Fujinaga Y, Watanabe T, Maruyama M, Muraki T, Takahashi M, Fujita A, Fujita S, Kurozumi M, Ueda K, Hamano H, Kawa S, Kadoya M.
  • Journal Title: Pancreatology Volume: 17 Issue: 4 Pages: 567-571
  • DOI: 10.1016/j.pan.2017.05.001
  • Peer Reviewed
• [Journal Article] Serum IgG4 Concentration in IgG4-Related Disease. (2017)
  • Author(s): Kawa S, Skold M, Ramsden DB, Parker A, Harding SJ.
  • Journal Title: Clin Lab. Volume: 63 Issue: 09/2017 Pages: 1323-1337
  • DOI: 10.7754/clin.lab.2017.170403
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical features of IgG4-related periaortitis/periarteritis based on the analysis of 179 patients with IgG4-related disease: a case-control study. (2017)
  • Author(s): Ozawa M, Fujinaga Y, Asano J, Nakamura A, Watanabe T, Ito T, Muraki T, Hamano H, Kawa S.
  • Journal Title: Arthritis Res Ther. Volume: - Issue: 1
  • DOI: 10.1186/s13075-017-1432-8
  • Peer Reviewed / Open Access
• [Journal Article] New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. (2017)
  • Author(s): Yamada K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, Hara S, Takahashi H, Nomura H, Kawa S, Kawano M.
  • Journal Title: Arthritis Res Ther Volume: 19 Issue: 1 Pages: 262-271
  • DOI: 10.1186/s13075-017-1467-x
  • Peer Reviewed / Open Access
• [Journal Article] Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients. (2017)
  • Author(s): Kubota K, Kamisawa T, Okazaki K, Kawa S, Hirano K, Hirooka Y, Uchida K, Shiomi H, Ohara H, Shimizu K, Arakura N, Kanno A, Sakagami J, Itoi T, Ito T, Ueki T, Nishino T, Inui K, Mizuno N, Yoshida H, Sugiyama M, Iwasaki E, Irisawa A, Shimosegawa T, Takeyama Y, Chiba T.
  • Journal Title: J Gastroenterol. Volume: 52 Issue: 8 Pages: 955-964
  • DOI: 10.1007/s00535-016-1302-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] International consensus for the treatment of autoimmune pancreatitis. (2017)
  • Author(s): Okazaki K, Chari ST, Frulloni L, Lerch MM, Kamisawa T, Kawa S, Kim MH, Levy P, Masamune A, Webster G, Shimosegawa T.
  • Journal Title: Pancreatology Volume: 17 Issue: 1 Pages: 1-6
  • DOI: 10.1016/j.pan.2016.12.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Immunobiology of Immunoglobulin G4 and Complement Activation Pathways in IgG4-Related Disease (2017)
  • Author(s): Kawa S
  • Journal Title: Curr Top Microbiol Immunol Volume: 401 Pages: 61-73
  • DOI: 10.1007/82_2016_39
  • ISBN: 9783319525419, 9783319525426
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunogenetics of IgG4-Related AIP (2017)
  • Author(s): Ota, M. Umemura, T. Kawa, S.
  • Journal Title: Curr Top Microbiol Immunol Volume: 401 Pages: 35-44
  • DOI: 10.1007/82_2016_37
  • ISBN: 9783319525419, 9783319525426
  • Peer Reviewed
• [Journal Article] Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification. (2016)
  • Author(s): Kanai K, Maruyama M, Kameko F, Kawasaki K, Asano J, Oguchi T, Watanabe T, Ito T, Muraki T, Hamano H, Matsumoto A, Arakura N, Kawa S
  • Journal Title: Pancreas Volume: 45 Issue: 8 Pages: 1189-9
  • DOI: 10.1097/mpa.0000000000000598
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Current Concepts and Diagnosis of IgG4-Related Pancreatitis (Type 1 AIP). (2016)
  • Author(s): Kawa S
  • Journal Title: Semin Liver Dis Volume: 36 Issue: 03 Pages: 257-73
  • DOI: 10.1055/s-0036-1584318
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Investigation of Susceptibility Genes Triggering Lachrymal/Salivary Gland Lesion Complications in Japanese Patients with Type 1 Autoimmune Pancreatitis. (2016)
  • Author(s): Oguchi T, Ota M, Ito T, Hamano H, Arakura N, Katsuyama Y, Meguro A, Kawa S
  • Journal Title: PLoS One Volume: - Issue: 1 Pages: e0146738-e0146738
  • DOI: 10.1371/journal.pone.0146738
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association Between Immunoglobulin G4-related Disease and Malignancy within 12 Years after Diagnosis: An Analysis after Longterm Followup. (2015)
  • Author(s): Asano J, Watanabe T, Oguchi T, Kanai K, Maruyama M, Ito T, Muraki T, Hamano H, Arakura N, Matsumoto A, Kawa S.
  • Journal Title: J Rheumatol. Volume: 42 Issue: 11 Pages: 2135-42
  • DOI: 10.3899/jrheum.150436
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autoimmune pancreatitis complicated with inflammatory bowel disease and comparative study of type 1 and type 2 autoimmune pancreatitis. (2015)
  • Author(s): Kawa S, Okazaki K, Notohara K, Watanabe M, Shimosegawa T
  • Journal Title: J Gastroenterol. Volume: 50 Issue: 7 Pages: 805-15
  • DOI: 10.1007/s00535-014-1012-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2011. (2015)
  • Author(s): Kanno A, Masamune A, Okazaki K, Kamisawa T, Kawa S, Nishimori I, Tsuji I, Shimosegawa T
  • Journal Title: Pancreas. Volume: 44 Pages: 535-9
  • Peer Reviewed
• [Journal Article] Extracorporeal shock wave lithotripsy treatment of pancreatic stones complicated with advanced stage autoimmune pancreatitis. (2015)
  • Author(s): Maruyama M, Watanabe T, Kanai K, Oguchi T, Asano J, Ito T, Muraki T, Hamano H, Arakura N, Uehara T, Kawa S.
  • Journal Title: BMC Gastroenterol. Volume: Mar 10;15:28 Issue: 1
  • DOI: 10.1186/s12876-015-0255-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] International consensus guidance statement on the management and treatment of IgG4-related disease. (2015)
  • Author(s): Khosroshahi A, Wallace ZS, Crowe JL, Kawa S, Stone JH.et al.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Issue: 7 Pages: 1688-99
  • DOI: 10.1002/art.39132
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 自己免疫性膵炎に対する経口ステロイド維持療法3年後の再燃予測因子について (2017)
  • Author(s): 中村晃、北野真希子、浅野純平、渡邉貴之、伊藤哲也、村木崇、浜野英明、川茂幸
  • Organizer: 第48回 日本膵臓学会大会
• [Presentation] Recollections of IgG4 study at Shinshu University (2017)
  • Author(s): Shigeyuki Kawa
  • Organizer: The International Pancreas Research Forum 2017
  • Int'l Joint Research
• [Presentation] 自己免疫性膵炎の長期予後 (2016)
  • Author(s): 浅野純平、伊藤哲也、川茂幸
  • Organizer: 第58回日本消化器病学会大会
  • Place of Presentation: 神戸、神戸コンベンションセンター
  • Year and Date: 2016-11-04
• [Presentation] Consensus for treatment of autoimmune pancreatitis. Prediction of long-term outcome for autoimmune pancreatitis. (2016)
  • Author(s): Kawa S
  • Organizer: International Association of Pancreatology 2016 (IAP 2016)
  • Place of Presentation: Sendai, Japan, Sendai International Center
  • Year and Date: 2016-08-04
  • Int'l Joint Research
• [Presentation] Long-term outcome of autoimmune pancreatitis with low serum IgG4 (2016)
  • Author(s): Asano J, Ito T, Nakamura A, Oguchi T, Kanai K, Watanabe T, Muraki T, Hamano H, Arakura N, Kawa S
  • Organizer: International Association of Pancreatology 2016 (IAP 2016)
  • Place of Presentation: Sendai, Japan, Sendai International Center
  • Year and Date: 2016-08-04
  • Int'l Joint Research
• [Presentation] International Session (symposium) 2: Recent progress in IgG4-related pancreatobiliar diseases. Prognosis and long-term outcomes of autoimmune pancreatitis. (2015)
  • Author(s): Kawa S, Maruyama M, Arakura N.
  • Organizer: JDDW2015
  • Place of Presentation: Tokyo, Grand Prince Hotel New Takanawa
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] 自己免疫性膵炎長期経過例における膵石灰化の要因｣、パネルデスカッション1：自己免疫性膵炎治療の現状と課題 (2015)
  • Author(s): 伊藤哲也、丸山真弘、浅野順平、小口貴也、金井圭太、新倉則和、川茂幸.
  • Organizer: 第46回日本膵臓学会大会2015
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-06-19
• [Presentation] ｢膵外胆管病変を有するIgG4関連硬化性胆管炎の検討｣、パネルデスカッション12：PSCとIgG4-SC:わが国の現状と最適治療を目指して (2015)
  • Author(s): 小口貴也、伊藤哲也、川茂幸.
  • Organizer: 第101日本消化器病学会総会
  • Place of Presentation: 仙台、仙台国際センター
  • Year and Date: 2015-04-25
• [Book] The Pancreas. 3rd ed (2018)
  • Author(s): Shigeyuki Kawa
  • Total Pages: 1173
  • Publisher: Willey Blackwell
  • ISBN: 9781119188391
• [Book] IgG4-related kidney disease (2016)
  • Author(s): Kawa S
  • Total Pages: 311
  • Publisher: Springer Japan
• [Book] 最新IgG4関連疾患 (2015)
  • Author(s): 岡崎和一、川茂幸、監修
  • Total Pages: 178
  • Publisher: 診断と治療社
• [Book] IgG4関連疾患 実践的臨床から病因へ (2015)
  • Author(s): 川 茂幸、川野充弘、編集
  • Total Pages: 206
  • Publisher: 前田書店