Antigen specific therapy for rheumatoid arthritis

• Project/Area Number: 15K19565
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: HIROTA Tomoya 筑波大学, 附属病院, 病院講師 (30742845)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節リウマチ / Altered Peptide Ligand / GPI / グルコース-6-リン酸イソメラーゼ

Outline of Final Research Achievements

To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (GPI) in mice model of GPI-induced arthritis (GIA).
Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies. APL12-TG rice seeds improved the histopathological arthritis scores and decreased IL-17 production. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4+CD25+Foxp3+ cells in the spleen.
APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.

Research Products

• [Journal Article] Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase. (2017)
  • Author(s): Hirota T, Tsuboi H, Iizuka-Koga M, Takahashi H, Asashima H, Yokosawa M, Kondo Y, Ohta M, Wakasa Y, Matsumoto I, Takaiwa F, Sumida T
  • Journal Title: Modern Rheumatology Volume: 印刷中 Issue: 3 Pages: 457-465
  • DOI: 10.1080/14397595.2016.1218598
  • Peer Reviewed
• [Presentation] Altered Peptide Ligand発現米を用いたGPIペプチド誘導関節炎の抑制効果の検討 (2016)
  • Author(s): 廣田智哉、坪井洋人、高橋広行、浅島弘充、若佐雄也、松本功、高岩文雄、住田孝之
  • Organizer: 第44回日本臨床免疫学会
  • Place of Presentation: 京王プラザ（東京都新宿区）
  • Year and Date: 2016-09-08
• [Presentation] Altered Peptide Ligand発現米を用いたGPIペプチド誘導関節炎の抑制効果の検討 (2016)
  • Author(s): 廣田智哉、坪井洋人、高橋広行、浅島弘充、若佐雄也、松本功、高岩文雄、住田孝之
  • Organizer: 第60回日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
• [Presentation] Altered Peptide Ligand発現米を用いたGPIペプチド誘導関節炎の抑制効果の検討 (2016)
  • Author(s): 廣田智哉、坪井洋人、飯塚麻菜、高橋広行、浅島弘充、若佐雄也、高岩文雄、松本功、住田孝之
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-04-21
• [Presentation] Altered Peptide Ligand発現米を用いたGPIペプチド誘導関節炎の抑制効果の検討 (2015)
  • Author(s): 廣田智哉、坪井洋人、飯塚麻菜、高橋広行、浅島弘充、若佐雄也、高岩文雄、松本功、住田孝之
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 札幌 コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] Altered Peptide Ligand発現米を用いたGPIペプチド誘導関節炎の抑制効果の検討 (2015)
  • Author(s): 廣田智哉、坪井洋人、飯塚麻菜、高橋広行、浅島弘充、若佐雄也、高岩文雄、松本功、住田孝之
  • Organizer: 第59回日本リウマチ学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-23