Clinical significance of anti-disulfide isomerase based on the AIRE research

• Project/Area Number: 25670461
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyushu University
• Principal Investigator: NAGAFUCHI Seiho 九州大学, 医学(系)研究科(研究院), 教授 (00150441)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自己免疫調節遺伝子 / 自己抗体 / 自己免疫疾患 / Disulfide Isomerase / 自己免疫性膵炎 / Protein Isomerase

Outline of Final Research Achievements

Since we found auto antigen in Aire knockout mice associated with autoimmune pancreatitis was disulfide isomerase (DI), we conducted human anti-DI antibody detection study in various autoimmune diseases, including autoimmune pancreatitis, gastritis, primary biliary cirrhosis, sjogren syndrome and autoimmune retinitis. We developed western blot system as well as enzyme linked immunosorbent assay. we screened 200 cases, however, we could not detect any autoantibody. It was suggested improvement of assay system to detect anti-DI is essentially important and the study should be continued to solve the problems.

Research Products

• [Journal Article] Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes. (2015)
  • Author(s): Izumi K, Mine K, Inoue Y, Teshima M, Ogawa S, Kai Y, Kurafuji T, Hirakawa K, Miyakawa D, Ikeda H, Inada A, Hara M, Yamada H, Akashi K, Niho Y, Ina K, Kobayashi T, Yoshikai Y, Anzai K, Yamashita T, Minagawa H, Fujimoto S, Kurisaki H, Shimoda K, Katsuta H, Nagafuchi S.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms7748
  • Peer Reviewed / Open Access
• [Journal Article] TYK2 promoter variant and diabetes mellitus in the Japanese. (2015)
  • Author(s): Nagafuchi S, Kamada Y, Hirakawa K , Tsutsu N, eet al.
  • Journal Title: EBioMedicine Volume: 2
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells. (2014)
  • Author(s): 13.Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.da, T., Hirata, S., Takamatsu, K., Haruta, M., Tsukamoto, H., Ito, T., Uchino, M., Ando, Y., Nagafuchi, S., Nishimura, Y., Senju, S.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e115198-e115198
  • DOI: 10.1371/journal.pone.0115198
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autoimmune gastro-pancreatitis with anti-protein disulfide isomerase-associated 2 autoantibody in Aire-deficient BALB/cAnN mice. (2013)
  • Author(s): Kurisaki H Yukihiro Nagao Y, Nagafuchi S, Mitsuyama M.
  • Journal Title: PLos One Volume: 8 Issue: 5 Pages: e82-e82
  • DOI: 10.1371/journal.pgen.0030082
  • Peer Reviewed
• [Journal Article] Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b. (2013)
  • Author(s): Matsuo T, Noguchi Y, Shindo M, Morita Y, Oda Y, Yoshida E, Hamada H, Harada M, Shiokawa Y, Nishida T, Tominaga R, Kikushige Y, Akashi K, Kudoh J, Shimizu N, Tanaka Y, Umemura T, Taniguchi T, Yoshimura A, Kobayashi T, Mitsuyama M, Kurisaki H, Katsuta H, Nagafuchi S.
  • Journal Title: Gene Volume: 530 Pages: 19-25
  • Peer Reviewed
• [Presentation] The role of TNFa pathway and microRNA in regulating autoimmune regulator gene expression and translatio (2013)
  • Author(s): Morita Y, Oda Y, Matsuo T, Kurisaki H, katsuta H, Nagafuchi S
  • Organizer: Immunolgy 2013, The 100th Annual Meeting of the American Assoiation of Immunologist (AAI)
  • Place of Presentation: Honolulu, Hawai, U.S.A.
• [Presentation] Regulatory mechanisms off autoimmune regulator (AIRE) gene and protein expression in central and peripheral immune system (2013)
  • Author(s): Morita Y, Matsuo T,Oda Y, Noguchi Y, Kurisaki H, katsuta H, Nagafuchi S
  • Organizer: 73rd Annual Meeting of the American Assoiation of Diabtest (ADA), 2013
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] ヒト胸腺および末梢血におけるAIRE遺伝子・蛋白の発現とその制御メカニズム
  • Author(s): 森田賢史、栗崎宏憲、勝田仁、永淵正法
  • Organizer: 第54回日本臨床ウイルス学会
  • Place of Presentation: 倉敷市
• [Remarks] 永淵研ホームページ
  • URL: http://www.shs.kyushu-u.ac.jp/nagafuchi/