Novel therapeutic strategies for multiple sclerosis targeting autoantibodies against talin.

• Project/Area Number: 15K09333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Chiba University
• Principal Investigator: Masahiro Mori 千葉大学, 大学院医学研究院, 准教授 (70345023)
• Co-Investigator(Kenkyū-buntansha): 鵜沢 顕之 千葉大学, 医学部附属病院, 助教 (10533317) ; 日和佐 隆樹 千葉大学, 大学院医学研究院, 准教授 (30260251)
• Research Collaborator: UCHIDA Tomohiko 千葉大学, 大学院医学研究院, 医員 ; MASUDA Hiroki 千葉大学, 大学院医学研究院, 特任助教 ; OHTANI Ryouhei 千葉大学, 大学院医学研究院, 医員 ; LIU Jia 千葉大学, 大学院医学研究院, 大学院生 ; SUGIMOTO Manabu 千葉大学, 大学院医学研究院, 大学院生
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 多発性硬化症 / talin-1 / 自己抗体 / 神経免疫疾患 / SEREX法 / ｔａｌｉｎ１ / 抗talin-1抗体 / バイオマーカー / talin / プロテインアレイ法 / SEREX

Outline of Final Research Achievements

We measured titers of antibodies against talin-1(TLN1) identified by SEREX and concentrations of soluble form of TLN1 (sTLN1) in large scale of multiple sclerosis (MS) patients, and normal controls. The results showed both anti-TLN1 antibody titers and sTLN1 were significantly higher in MS patients than in normal controls. In conclusion, novel autoantibodies against TLN1 can be found in sera from some MS patients; the production of serum anti-TLN1 antibody in MS is thought to be caused not by response to elevation of sTLN1.

Research Products

• [Journal Article] Serum soluble Talin-1 levels are elevated in patients with multiple sclerosis, reflecting its disease activity. (2017)
  • Author(s): Mayumi Muto, Masahiro Moti, Jia Liu, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Kazuo Sugimoto, Sathoshi Kuwabara
  • Journal Title: Journal of Neuroimmunology Volume: 305 Pages: 131-134
  • DOI: 10.1016/j.jneuroim.2017.02.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction (2017)
  • Author(s): Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
  • Journal Title: Oncotarget Volume: 9 Issue: 5 Pages: 5600-5613
  • DOI: 10.18632/oncotarget.23789
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel serum autoantibodies against talin1 in multiple sclerosis: Possible pathogenetic roles of the antibodies (2015)
  • Author(s): Muto M, Mori M, Hiwasa T, Takiguchi M, Iwadate Y, Uzawa A, Uchida T, Masuda H, Sugimoto K, Kuwabara S.
  • Journal Title: Journal of Neuroimmunology Volume: 284 Pages: 30-36
  • DOI: 10.1016/j.jneuroim.2015.05.005
  • NAID: 120007088198
  • Peer Reviewed / Open Access
• [Presentation] SOLUBLE TALIN-1 AND ANTI-TALIN-1 ANTIBODY ARE ASSOCIATED WITH PATHOGENESIS OF MULTIPLE CLEROSIS AND MAY BE AS BIOMARKER FOR THE DISEASE. (2017)
  • Author(s): L. Jia, M. Muto, M. Mori, A. Uzawa, T. Uchida, H. Masuda, R. Ohtani, K. Sugimoto, S. Kuwabara.
  • Organizer: The XXIII World Congress of Neurology (WCN 2017)
  • Int'l Joint Research
• [Presentation] 多発性硬化症患者血清中の新規自己抗体：抗talin1抗体 (2015)
  • Author(s): 森 雅裕
  • Organizer: 日本神経免疫学会
  • Place of Presentation: 長良川国際会議場（岐阜県土岐市）
  • Year and Date: 2015-09-15