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Analysis of the mechanisms of intravenous immunoglobulin-resistant Kawasaki disease using iPS cell technology

Research Project

Project/Area Number 25461604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ikeda Kazuyuki  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30507786)

Co-Investigator(Kenkyū-buntansha) HAMAOKA Kenji  京都府立医科大学, 大学院医学研究科, 教授 (60189602)
OSAFUNE Kenji  京都大学, iPS細胞研究所, 教授 (80502947)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords川崎病 / iPS細胞 / IVIG不応 / ガンマグロブリン不応 / 血管内皮細胞 / マイクロアレイ法 / 新規疾患モデル / ガンマグロブリン療法(IVIG) / IVIG不応川崎病 / マイクロアレイ
Outline of Final Research Achievements

Objective: This study clarifies the mechanisms of IVIG resistance in Kawasaki disease (KD) using an iPSC disease model.
Methods and Results:Dermal fibroblasts or PBMNCs from two IVIG-resistant and two IVIG-responsive KD patients were reprogrammed by the episomal vector-mediated transduction of reprogramming factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG-responsive KD patients were compared by RNA-sequencing analyses. We found that the expression of chemokine X was significantly up-regulated in iPSC-ECs from IVIG-resistant KD patients. Additionally, GSEA revealed that gene sets involved in IL-6 signaling were also up-regulated.
Conclusions:Our mechanistic analyses suggest that chemokine X, which plays a role in leukocyte transmigration, is a candidate key molecule for IVIG resistance. They also indicate that up-regulation of IL-6 related genes may be involved in this pathogenesis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (3 results)

  • [Journal Article] Oxidative Stress in Kawasaki Disease Vasculitis.2015

    • Author(s)
      Hamaoka K, Yahata T, Okamoto A, Suzuki C, Kuchitsu Y, Yoshioka A, Ikeda K
    • Journal Title

      International Journal of Pediatrics & Neonatal Care

      Volume: 1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The involvement of the vasa vasorum in the development of vasculitis in animal model of KD2014

    • Author(s)
      Hamaoka-Okamoto A, Suzuki C, Yahata T, Ikeda K, Hamaoka K
    • Journal Title

      Pediatr Rheumatol Online J

      Volume: 30

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Platelet activation dynamics evaluated using platelet-derived microparticles in Kawasaki disease.2014

    • Author(s)
      Yahata T, Suzuki C, Yoshioka A, Hamaoka A, Ikeda K.
    • Journal Title

      Circ J.

      Volume: 78 Pages: 188-193

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 京都地区におけるステロイド初期併用療法の効果検証~RAISE不応重症川崎病の経験2015

    • Author(s)
      池田和幸、鈴木千夏、八幡倫代、朽津有紀、岡本亜希子、小澤誠一郎、松尾憲典、足立晋介、内藤岳史、濵岡 建城
    • Organizer
      第35回日本川崎病学会・学術集会
    • Place of Presentation
      鹿児島県医師会館
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血小板凝集能測定による川崎病冠動脈後遺症例に対するdual antiplatelet therapy(DAPT)の有用性の検討2015

    • Author(s)
      池田和幸、鈴木千夏、八幡倫代、朽津有紀、岡本亜希子、濱岡建城
    • Organizer
      第51回日本小児循環器学会・学術集会
    • Place of Presentation
      ホテル日航東京
    • Year and Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Kawasaki Disease. Overview of Revised Japanese Guideline and clarification of immunopathogenesis of KD using iPS cell technology2015

    • Author(s)
      Ikeda K
    • Organizer
      The sixth China-Japan Children Summit Forum
    • Place of Presentation
      Shanghai Children's hospital
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of the mechanisms of intravenous immunoglobulin-resistant Kawasaki disease using iPS cell technology2015

    • Author(s)
      Ikeda K, Ameku T, Nomiya Y, Nakamura M, Mae S, Matsui S, Yahata T, Okamoto-Hamaoka A, Suzuki C, Kuchitsu Y, Watanabe A, Osafune K, Hamaoka K
    • Organizer
      49th Annual Meeting of the Association for European Paediatric and Congenital Cardiology
    • Place of Presentation
      Prague Congress Centre
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the mechanisms of intravenous immunoglobulin-resistant Kawasaki disease using iPS cell2015

    • Author(s)
      Ikeda K, Ameku T, Matsui S, Yahata T, Okamoto-Hamaoka A, Suzuki C, Yoshioka A, Kuchitsu Y, Watanabe A, Osafune K, Hamaoka K
    • Organizer
      International Kawasaki disease Symposium
    • Place of Presentation
      Honolulu, Hawaii
    • Year and Date
      2015-02-03 – 2015-02-06
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of the mechanisms of intravenous immunoglobulin-resistant Kawasaki disease using iPS cell2014

    • Author(s)
      Ikeda K, Ameku T, Matsui S, Yahata T, Okamoto-Hamaoka A, Suzuki C, Yoshioka A, Kuchitsu Y, Watanabe A, Osafune K, Hamaoka K
    • Organizer
      American Heart Association
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞由来血管内皮細胞を用いたガンマグロブリン不応川崎病の病態解明2014

    • Author(s)
      池田和幸、天久朝廷、松井敏、八幡倫代、岡本亜希子、鈴木千夏、朽津有紀、渡辺亮、長船健二、濱岡建城
    • Organizer
      第34回日本川崎病学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞技術を用いたガンマグロブリン不応川崎病の病態解明2014

    • Author(s)
      池田和幸、天久朝廷、松井敏、八幡倫代、岡本亜希子、鈴木千夏、長船健二、濱岡建城
    • Organizer
      第117回日本小児科学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-04-11 – 2014-04-13
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞技術を用いたガンマグロブリン不応川崎病の病態解明2014

    • Author(s)
      池田和幸、天久朝廷、松井敏、八幡倫代、岡本亜希子、鈴木千夏、長船健二、濱岡建城
    • Organizer
      第117回日本小児科学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] iPS細胞技術を用いたガンマグロブリン不応川崎病の病態解明2013

    • Author(s)
      池田和幸、天久朝廷、松井敏、八幡倫代、岡本亜希子、鈴木千夏、長船健二、濱岡建城
    • Organizer
      第49回日本小児循環器学会
    • Place of Presentation
      国立オリンピック記念青少年総合センター
    • Related Report
      2013 Research-status Report
  • [Presentation] iPS細胞技術を用いたガンマグロブリン不応川崎病の病態解明2013

    • Author(s)
      池田和幸、天久朝廷、松井敏、八幡倫代、岡本亜希子、鈴木千夏、長船健二、濱岡建城
    • Organizer
      第33回日本川崎病学会学術集会
    • Place of Presentation
      富山国際会議場
    • Related Report
      2013 Research-status Report
  • [Book] 今日の小児治療指針第16版(分担執筆)2015

    • Author(s)
      濱岡建城、池田和幸
    • Total Pages
      1006
    • Publisher
      医学書院
    • Related Report
      2015 Annual Research Report
  • [Book] 別冊日本臨床「免疫症候群Ⅰ」 第2版(分担執筆)2015

    • Author(s)
      池田和幸、濱岡建城
    • Total Pages
      931
    • Publisher
      日本臨床社
    • Related Report
      2015 Annual Research Report
  • [Book] 特集 川崎病 ー基礎・臨床研究の最新知見ー2014

    • Author(s)
      池田和幸、濱岡建城
    • Total Pages
      7
    • Publisher
      日本臨床社
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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