Investigation of biomarkers to select the optimal disease-modifying drugs for each individual patient with multiple sclerosis.

• Project/Area Number: 16K21285
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology; Medical pharmacy
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Fujii Chihiro 京都府立医科大学, 医学部附属病院, 研究員 (00516065)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 多発性硬化症 / フィンゴリモド / T細胞 / バイオマーカー / CD56陽性T細胞 / fingolimod / 細胞障害性分子 / IFN‐γ / MBP反応性T細胞 / IFN-γ / 疾患修飾薬 / 免疫学

Outline of Final Research Achievements

We found that the frequency of CD56+ T cells in peripheral blood increased in fingolimod-treated patients with multiple sclerosis. These T cells expressed cytotoxic molecules and showed a Th1-like response. In addition, the CD56+ T cells produced IFN-γ in response to myelin basic protein. The elevated frequency of CD56+ T cells in fingolimod-treated patients was further increased at relapse. Relapse-experienced patients retained a higher frequency of CD56+ T cells even during remission compared to patients who did not have any relapse while on fingolimod treatment.
Our results showed that the T cell phenotypes were altered under fingolimod therapy,and raised a possibility that the frequency of CD56+ T cells is a useful biomarker for predicting and detecting relapses, although further confirmation is required.

Research Products

• [Presentation] Elevated frequency of CD56+ T cells in neuromyelitis optica spectrum disorder and multiple sclerosis with “Red flags”. (2017)
  • Author(s): Fujii C, Kondo T, Ochi H, Okada Y, Hashi Y, Matsumoto S, Takahashi R, Nakagawa M, Mizuno T.
  • Organizer: The 23rd World Congress of Neurology (WCN) 2017. Kyoto, Japan
  • Int'l Joint Research
• [Presentation] Association of red flags with therapeutic reactivity in Multiple sclerosis. (2017)
  • Author(s): Ashida S, Hamatani M, Ochi H, Fujii C, Okada Y, Hashi Y, Kawamura K, Matsumoto S, Kusaka H, Takahashi R, Nakagawa M, Mizuno T, Kondo T.
  • Organizer: The 23rd World Congress of Neurology (WCN) 2017. Kyoto, Japan
  • Int'l Joint Research
• [Presentation] 多発性硬化症におけるRed Flagsと治療反応性の検討 (2017)
  • Author(s): 芦田真士, 濱谷美緒, 藤井ちひろ, 岡田洋一郎, 端祐一郎, 松本禎之, 水野敏樹, 中川正法, 高橋良輔, 近藤誉之
  • Organizer: 第29回日本神経免疫学会 北海道
• [Presentation] CD56 positivity of T cells as a candidate of a predictive biomarker for relapse of multiple sclerosis under fingolimod therapy. (2016)
  • Author(s): Chihiro Fujii
  • Organizer: 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis（ECTRIMS）
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-15
• [Presentation] Fingolimod治療下多発性硬化症の再発例におけるCD56+T細胞の経時的変化. (2016)
  • Author(s): 藤井 ちひろ
  • Organizer: 第57 回日本神経学会学術集会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2016-05-19