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Determination of disease characteristics of Castleman's disease and Rheumatoid arthritis using serum cytokine and chemokine patterns.

Research Project

Project/Area Number 20K10460
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionLouis Pasteur Center for Medical Research

Principal Investigator

Uno Kazuko  公益財団法人ルイ・パストゥール医学研究センター, IFN・生体防御研究室, 研究員(移行) (50211082)

Co-Investigator(Kenkyū-buntansha) 吉崎 和幸  大阪大学, 産業科学研究所, 特任教授 (90144485)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsIL-6 / トシリズマブ / サイトカイン / ケモカイン / PLS2解析 / キャッスルマン病 / 関節リウマチ / COVID-19 / TCZ:トシリズマブ / PLS解析 / 多中心性キャッスルマン病 / 炎症性ケモカイン / Multi-plex / 血中サイトカイン / リウマチ / 疾患分類
Outline of Research at the Start

健常人の状態と比較しつつ、キャッスルマン病および類縁疾患やリウマチ患者の抗体療法前後の血清中のサイトカイン・ケモカインをMulti-plex法により多項目測定し、そのパターンから疾患分類、また治療前に効果的な治療薬の予測のバイオマーカーの特定を目指す。解析方法としては説明変数(記述子)の数がサンプルの数より多くても計算可能で、回帰式を作るときにノイズの影響を受けにくく、説明変数の間の相関が高くても対応可能なPLS2解析を用いる予定である。

Outline of Final Research Achievements

Rheumatoid arthritis, Castleman's disease, and COVID-19 can be effectively treated with Tocilizumab(TCZ), an antihuman IL-6 receptor antibody drug that inhibits the action of IL-6. The pathogenesis of all three disease are different: rheumatoid arthritis is an autoimmune disease, Castleman's disease is a lymphoproliferative disease, and COVID-19 is an infectious disease. We comprehensively measured cytokine/chemokines in the blood serum of patients before/after TCZ treatments and compared all three diseases with the serum of healthy subjects.
By clarifying the cytokine/chemokine system affected by TCZ in each disease, the effect of treatment and changes in cytokine/chemokine dynamics, will reveal how IL-6 is involved in the clinical symptoms, and whether blocking IL-6 can result in significant improvements or the elimination of these symptoms.

Academic Significance and Societal Importance of the Research Achievements

リウマチとキャッスルマン病、COVID-19はIL-6の作用を抑制する抗ヒトIL-6受容体の抗体薬(TCZ:トシリズマブ)による治療が有効であるが、病因は全く異なる疾患である。各疾患のTCZ治療前後でのサイトカイン・ケモカインの動態を測定し、その変化を解析する事により、TCZの各疾患に対する作用を明らかにする。また、各疾患の特性にせまることが可能となる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2N protein2022

    • Author(s)
      Nakayama Emi E.、Kubota-Koketsu Ritsuko、Sasaki Tadahiro、Suzuki Keita、Uno Kazuko、Shimizu Jun、Okamoto Toru、Matsumoto Hisatake、Matsuura Hiroshi、Hashimoto Shoji、Tanaka Toshio、Harada Hiromasa、Tomita Masafumi、Kaneko Mitsunori、Yoshizaki Kazuyuki、Shioda Tatsuo
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-022-12252-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 血中サイトカイン・ケモカインのPLS2解析による、キャッスルマン病と関節リウマチの疾患特性の解析2022

    • Author(s)
      宇野賀津子、吉崎和幸、岩橋充啓、原田博雄、金香充範、富田雅史、藤宮仁
    • Journal Title

      PASKEN J

      Volume: 2021 Pages: 29-35

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Prompt Reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-192021

    • Author(s)
      Hashimoto Shoji, Yoshizaki Kazuyuki, Uno Kazuko, et al
    • Journal Title

      Frontiers in Medicine

      Volume: 8 Pages: 1-16

    • DOI

      10.3389/fmed.2021.734838

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired HVJ-stimulated Interferon producing capacity in MPO-ANCA-Associated vasculitis with Rapidly Progressive Glomerulonephritis lead to susceptibility to infection2020

    • Author(s)
      95. Uno K, Muso E, Ito-Ihara T, Endo T, Yasuda Y, Yagi K, Suzuki K
    • Journal Title

      Cytokine

      Volume: Dec;136 Pages: 1-8

    • DOI

      10.1016/j.cyto.2020.155221

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 新型コロナ感染症とH1N1型インフルエンザの 血中サイトカイン・ケモカイン動態: PLS2解析法による疾患特性分析の試み2022

    • Author(s)
      宇野賀津子,吉崎和幸, 田中敏郎, 橋本章司, 原田博雅 金香充範, 冨田雅史, 中山英美, 塩田達雄 , 藤宮仁
    • Organizer
      第22回日本抗加齢医学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] トシリズマブ(TCZ)治療前後の血清サイトカイン・ケモカインを用いたPLS2解析によるCOVID-19, キャッスルマン病(iMCD) および間接リウマチの疾患特性の解析2022

    • Author(s)
      宇野賀津子,吉崎和幸, 田中敏郎, 橋本章司, 原田博雅 金香充範, 冨田雅史, 中山英美, 塩田達雄 , 藤宮仁
    • Organizer
      第50回臨床免疫学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Characterizing COVID-19, Castleman’s Disease and Rheumatoid Arthritis Based on Patients’ Serum Cytokine and Chemokine Patterns Before and After Tocilizumab Treatment Using Partial Least Squares Regression 2 Analysis2022

    • Author(s)
      Uno K, Yoshizaki K, Tanaka T, Hashimoto S, Iwahashi M, Nakayama E, Shiota T, Fujimiya H
    • Organizer
      Cytokines 2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] Comparing COVID-19 and H1N1 Influenza: Analyzing Cytokine and Chemokine Profiles2022

    • Author(s)
      Uno K, Yoshizaki K, Tanaka T, Hashimoto S, Harada H, Kaneko M, Tomita M, Nakayama E, Shiota T, Tsuchihashi Y, Fujimiya H
    • Organizer
      JSICR/MMCB 2022 Joint Symposium
    • Related Report
      2022 Annual Research Report
  • [Presentation] Tocilizumab treatment of COVID-19, Castleman’s Disease and Rheumatoid Arthritis: controlling IL-6 improves the pathology of diseases with a variety of etiologies2022

    • Author(s)
      Uno K, Yoshizaki K
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Disease Characterization of Castleman’s Disease and Rheumatoid Arthritis based on Serum Cytokine and Chemokine Patterns Using Partial Least Squares Regression 2 Analysis2021

    • Author(s)
      Kazuko Uno, Kazuyuki Yoshizaki, Mitsuhiro Iwahashi, Hitoshi Fujimiya
    • Organizer
      1st International Symposium on Castleman Disease
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Characterizing COVID-19, Castleman’s Disease and Rheumatoid Arthritis Based on Patients’ Serum Cytokine and Chemokine Patterns Before and After Tocilizumab Treatment Using Partial Least Squares Regression 2 Analysis2021

    • Author(s)
      K. Uno, H. Fujimiya, M. Iwahashi, S. Hashimoto, T. Tanaka, K. Yoshizaki
    • Organizer
      Cytokines 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterizing COVID-19, Castleman’s Disease and Rheumatoid Arthritis Based on Patients’ Serum Cytokine/Chemokine Patterns Before and After Tocilizumab Treatment Using Partial Least Squares Regression 2 Analysis2021

    • Author(s)
      Kazuko Uno, Toshio Tanaka, Kazuyuki Yoshizaki
    • Organizer
      The 50th Annual Meeting of the Japanese Society forImmunology
    • Related Report
      2021 Research-status Report
  • [Book] キャッスルマン病、TAFRO症候群(分担:多中心性キャッスルマン病のサイトカイン・ケモカイン特性)2022

    • Author(s)
      宇野賀津子(分担執筆)
    • Total Pages
      280
    • Publisher
      フジメディカル出版
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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