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Development of a new rheumatoid arthritis monitoring method by analysis of anti-CCP antibody-producing B cell repertoire

Research Project

Project/Area Number 17K08973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionTohoku University

Principal Investigator

ISHII Tomonori  東北大学, 大学病院, 特任教授 (10282138)

Co-Investigator(Kenkyū-buntansha) 小笠原 康悦  東北大学, 加齢医学研究所, 教授 (30323603)
白井 剛志  東北大学, 大学病院, 助教 (20646997)
藤井 博司  東北大学, 医学系研究科, 准教授 (30531321)
城田 祐子  東北医科薬科大学, 医学部, 准教授 (20455819)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords関節リウマチ / レパトア解析 / アバタセプト / TCRレパトア / BCRレパトア / BCRレパトア / 生物学的製剤 / 抗CCP抗体 / B細胞レパトア解析
Outline of Final Research Achievements

Abatacept was administered to 15 patients with rheumatoid arthritis who did not lose their activity despite existing treatment. Before treatment, peripheral blood was collected from patients and lymphocytes were separated from peripheral blood. Repertoire analysis of B cell receptor and T cell receptor was performed on the obtained lymphocytes. Abatacept was treated for more than three months in these patients. After treatment, a second repertoire analysis of B cells and T cells was performed and compared with the repertoire before treatment. Abatacept treatment was effective in 70% of patients. Specific T cell repertoire decreased before and after treatment in lymphocytes obtained from patients who responded to these treatments

Academic Significance and Societal Importance of the Research Achievements

本研究により、関節リウマチ患者における活動性と関連したTCRのレパトアが存在する事が解明された。またこうしたレパトアがアバタセプトの治療により正常化することが確認できた。これにより、治療前に、こうした特定のレパトアの存在の有無をみることで、治療前からアバタセプトの有効性が期待できる患者群を特定できることが可能性が示された。また、治療後にこうしたレパトアが改善したことをマーカーに治療方針を決定することができる可能性が示唆された。これにより、薬剤の効率的な使用が可能になり、無駄な治療をする確率を減らすことで、患者の安全性のみでなく社会経済的観点からも有用性が考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Insufficient Use of Corticosteroids without Immunosuppressants Results in Higher Relapse Rates in Takayasu Arteritis2019

    • Author(s)
      Mutoh Tomoyuki、Shirai Tsuyoshi、Fujii Hiroshi、Ishii Tomonori、Harigae Hideo
    • Journal Title

      The Journal of Rheumatology

      Volume: 47 Issue: 2 Pages: 255-263

    • DOI

      10.3899/jrheum.181219

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Four distinct clinical phenotypes of vasculitis affecting medium-sized arteries.2019

    • Author(s)
      Shirai T, Shirota Y, Fujii H, Ishii T, Harigae H.
    • Journal Title

      Scand J Rheumatol

      Volume: 48 Issue: 4 Pages: 1-7

    • DOI

      10.1080/03009742.2018.1551965

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Takayasu Arteritis Coexisting with Sclerosing Osteomyelitis2018

    • Author(s)
      Shirai T, Hanaoka R, Goto Y, Kojima I, Ishii Y, Hoshi Y, Fujita Y, Shirota Y, Fujii H, Ishii T, Harigae H.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 13 Pages: 1929-1934

    • DOI

      10.2169/internalmedicine.0329-17

    • NAID

      130007387190

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-07-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs2018

    • Author(s)
      Ojima Y, Sawada K, Fujii H, Shirai T, Saito A, Kagaya S, Aoki S, Takeuchi Y, Ishii T, Nagasawa T.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 9 Pages: 1301-1308

    • DOI

      10.2169/internalmedicine.9848-17

    • NAID

      130006730798

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-05-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period2018

    • Author(s)
      Ogata A1,2, Tanaka Y, Ishii T, Kaneko M, Miwa H, Ohsawa S; SHINOBI study group.
    • Journal Title

      Mod Rheumatol

      Volume: 28 Issue: 1 Pages: 76-84

    • DOI

      10.1080/14397595.2017.1332507

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term safety and efficacy of weekly subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis who had an inadequate response to subcutaneous tocilizumab every other week: Results from the open-label extension of the SHINOBI study2018

    • Author(s)
      Ogata A, Tanaka Y, Ishii T, Kaneko M, Miwa H, Ohsawa S, Yamakawa R
    • Journal Title

      Mod Rheumatol

      Volume: Epub ahead of print Issue: 5 Pages: 767-774

    • DOI

      10.1080/14397595.2018.1533514

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus.2018

    • Author(s)
      Ishii T, Tanaka Y, Kawakami A, Saito K, Ichinose K, Fujii H, Shirota Y, Shirai T, Fujita Y, Watanabe R, Chiu SW, Yamaguchi T, Harigae H.
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 6 Pages: 1-7

    • DOI

      10.1080/14397595.2018.1432331

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bortezomib treatment induces a higher mortality rate in lupus model mice with a higher disease activity.2017

    • Author(s)
      Ikeda T, Fujii H, Nose M, Kamogawa Y, Shirai T, Shirota Y, Ishii T, Harigae H.
    • Journal Title

      Arthritis Research & Therapy

      Volume: 19(1) Issue: 1 Pages: 187-187

    • DOI

      10.1186/s13075-017-1397-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relapsing Polychondritis Complicated by Myelodysplastic Syndrome Is Resistant to Immunosuppression: Comment on the Article by Dion et al.2017

    • Author(s)
      Shirai T, Fujii H, Saito R, Nasu K, Kamogawa Y, Fukuhara N, Fujita Y, Shirota Y, Ishii T, Harigae H.
    • Journal Title

      Arthritis & Rheumatology

      Volume: 69 Issue: 3 Pages: 682-683

    • DOI

      10.1002/art.39969

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] SARILUMAB AND TOCILIZUMAB RECEPTOR OCCUPANCY (RO), AND EFFECTS ON C-REACTIVE PROTEIN (CRP) LEVELS, IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA),2019

    • Author(s)
      Christine Xu, Patrick Nolain, Qiang Lu, Anne Paccaly, Melitza Iglesias-Rodriguez, Gregory St John, Chad Nivens, Rafael Maldonado, Tomonori Ishii, Ernest Choy, Vanaja Kanamaluru
    • Organizer
      EULAR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sarilumab and Tocilizumab Receptor Occupancy (RO), and Effects on C-Reactive Protein (CRP) Levels, in Patients with Rheumatoid Arthritis (RA)2019

    • Author(s)
      Christine Xu, Patrick Nolain , Qiang Lu , Anne Paccaly , Melitza Iglesias-Rodriguez , Gregory St John , Chad Nivens , Rafael Maldonado , Tomonori Ishii , Ernest Choy and Vanaja Kanamaluru
    • Organizer
      ACR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 強皮症・MCTD・重複症候群1 全身性強皮症に伴う難治性皮膚潰瘍に対する低出力衝撃波療法の有効性・安全性検証試験2018

    • Author(s)
      石井 智徳(東北大学病院 臨床研究推進センター), 川口 鎮司, 石川 治, 竹森 弘光, 高澤 徳彦, 小林 仁, 安岡 秀剛, 高橋 裕一, 小寺 隆雄, 高井 修, 中屋 来哉, 泉山 朋政, 齋藤 真一郎, 鴨川 由起子, 藤田 洋子, 白井 剛志, 城田 祐子, 藤井 博司, 張替 秀郎
    • Organizer
      日本リウマチ学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 全国多施設前向きコホート研究(Apple study)を用いた関節リウマチ患者における機能的改善の予測因子に関する検討2018

    • Author(s)
      古賀 智裕, 日高 利彦, 岡田 覚丈, 荒牧 俊幸, 福田 孝昭, 高橋 裕一, 石井 智徳
    • Organizer
      九州リウマチ
    • Related Report
      2018 Research-status Report
  • [Presentation] リウマチ性疾患の合併症(感染症以外・アミロイドーシス・その他)3:その他2 膠原病性肺動脈性肺高血圧症(CTD-PAH)における予後予測因子と死因について2018

    • Author(s)
      城田 祐子, 星 陽介, 佐藤 紘子, 藤田 洋子, 白井 剛志, 藤井 博司, 石井 智徳, 張替 秀郎
    • Organizer
      日本リウマチ学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 全身性エリマトーデスにおける新規治療薬の開発戦略2017

    • Author(s)
      石井智徳
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Four-Distinct Phenotypes of Patients with Necrotizing Arteritis of Medium and Small Artery2017

    • Author(s)
      Ishii T, Kawaguchi Y, Ishikawa O, Takasawa N, Kodera T, Yasuoka H, Takahashi Y, Takai O, Nakaya I, Fujii H, Kamogawa Y, Shirota Y, Shirai T, Fujita Y, Saito S, Shimokawa H and Harigae H.
    • Organizer
      2017 ACR/ARHP Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 全身性強皮症における皮膚潰瘍2017

    • Author(s)
      石井 智徳
    • Organizer
      第32回日本臨床リウマチ学会
    • Related Report
      2017 Research-status Report
  • [Remarks] 東北大学 血液・免疫病学分野

    • URL

      http://www.rh.med.tohoku.ac.jp/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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