Induction of Peripheral immune tolerance in Myasthenia Gravis Patients

• Project/Area Number: 24590215
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TANAKA Sachiko 東京薬科大学, 薬学部, 助教 (50328556)
• Research Collaborator: MASUDA Masayuki ; INOUE Aya ; ITO Suguru ; AIZAWA Hitoshi
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 重症筋無力症 / 制御性B細胞 / B細胞活性化因子 / 免疫寛容 / IL-10 / CD24+CD38+CD19+制御性B細胞 / CD25+Foxp3+CD4+制御性T細胞 / 副腎皮質ステロイド剤 / カルシニューリン阻害剤 / オーダーメイド療法 / 重症筋無力症状

Outline of Final Research Achievements

Myasthenia gravis (MG) is an autoimmune disease which caused by producing anti-ACh-R antibody in plasma cells which was differentiated from B cells. In this study, we showed on B cell activating factor -receptor (BAFF-R) was highly expressed on CD19+ B cells in MG patients. We also evaluated the percentage of IL-10+ regulatory B (Breg) cells on B cells. In the MG patients, the frequency of Breg cells was lower than those in healthy subjects. There was a significant correlation between the expression levels of IL-10-R on B cells and the changing rate of anti ACh-R antibody titer in plasma. From these results, we suggest that BAFF attenuate to activate B cells and stimulate production of anti ACh-R antibody in MG patients. On the other hand, IL-10 affected B cells to suppress the secretion of the autoantibody. In conclusion, induction of peripheral immune tolerance would be useful for MG patients by suppression of BAFF production and induction of IL-10.

Research Products

• [Journal Article] 重症筋無力症患者におけるBAFFシグナル制御を標的とした新たな免疫抑制療法の可能性に関する検討 (2015)
  • Author(s): 田中 祥子 井上 文 増田 眞之 内海 裕也 平野 俊彦
  • Journal Title: 臨床薬理の進歩 Volume: 30 Pages: 60-64
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 重症筋無力症患者における治療効果予測因子としての末梢T・Bリンパ球の特徴付け (2014)
  • Author(s): 田中 祥子
  • Journal Title: 薬学研究の進歩 薬学研究奨励財団助成研究成果報告集 Volume: 30 Pages: 95-102
• [Presentation] 重症筋無力症患者における制御性B細胞と治療効果との関連 (2015)
  • Author(s): 田中 祥子，増田 眞之，落合 有美香，河合 奈々江，黒江 里歌，井上 文，伊藤 傑，相澤 仁志，明石 貴雄，恩田 健二，杉山 健太郎，平野 俊彦
  • Organizer: 第35回日本臨床薬理学会学術総会
  • Place of Presentation: 愛媛県 松山市
  • Year and Date: 2015-12-04 – 2015-12-06
• [Presentation] 重症筋無力症患者における制御性B細胞と治療効果との関連 (2014)
  • Author(s): 落合 有美香，田中 祥子，増田 眞之，近藤 智子，井上 文，伊藤 傑，明石 貴雄，相澤 仁志，杉山 健太郎，平野 俊彦
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 20140328-20140330
• [Presentation] B cell activating factor belonging to the tumor necrosis family were related to efficacy of glucocorticoid therapy in myasthenia gravis patients (2012)
  • Author(s): Sachiko Tanaka, Mamiko Yamamoto, Akemi Maeno, Yumika Ochiai, Suguru Ito, Masayuki Masuda, Kenji Onda, Kentaro Sugiyama, Hiroya Utsumi, Toshihiko Hirano
  • Organizer: The 33 rd the Annual Meating of the Japanese Society of Clinical Pharmacology and Therapeutics(BPS/JSCPT Joint Symposium)
  • Place of Presentation: Naha, Japan
  • Year and Date: 20121129-20121201
• [Presentation] Low-dose glucocorticoid therapy complement the pituitary-adrenocortical system and reduce anxiety and insomnia in myasthenia gravis patients (2012)
  • Author(s): Sachiko Tanaka, Takao Akashi,Suguru Itoh, Masayuki Masuda, Hiroya Utsumi, Chiho Kasahara, Yumika Ochiai, Mamiko Yamamoto, Hironori Takeuchi, Sakae Unezaki and Toshihiko Hirano
  • Organizer: The 72th World Congress of Pharmacy and Pharmaceutical Sciences
  • Place of Presentation: Amsterdam, Holland
  • Year and Date: 20121003-20121008