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Development of an immunological monitoring system to predict chronic rejection in kidney transplant recipients.

Research Project

Project/Area Number 18K09156
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionHokkaido University

Principal Investigator

Hotta Kiyohiko  北海道大学, 大学病院, 講師 (90443936)

Co-Investigator(Kenkyū-buntansha) 村上 正晃  北海道大学, 遺伝子病制御研究所, 教授 (00250514)
岩見 大基  北海道大学, 大学病院, その他 (80581115)
篠原 信雄  北海道大学, 医学研究院, 教授 (90250422)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords移植免疫 / 腎移植 / 慢性抗体関連型拒絶反応 / 早期診断 / Tリンパ球 / 長期成績 / リンパ球混合反応 / CD4陽性T細胞 / Bリンパ球 / 慢性抗体型拒絶反応
Outline of Final Research Achievements

Chronic active antibody-mediated rejection (CAAMR) is the main cause of graft loss in the long-term. Pathological changes during CAAMR occur gradually even without clinical manifestations, followed by dysregulation of the function of the kidney transplant. Therefore, a reliable immunoresponse monitoring system to identify recipients who will develop CAAMR in the future is required.
A mixed lymphocyte reaction (MLR) assay is a method to measure T cells alloreactivity via direct pathway (DP). Recent studies indicate that DP also contribute the pathogenesis of chronic injury. However, there are no reports of MLR assay to monitor CAAMR. Therefore, we tried to develop a novel MLR monitoring system that predicts CAAMR in kidney transplant recipients. To this end, we measured the anti-donor response using our novel MLR in 150 kidney recipients whose graft status were evaluated by graft biopsy and analyzed the relationship between the anti-donor response and pathological findings of allograft.

Academic Significance and Societal Importance of the Research Achievements

腎移植長期成績の向上にCAAMRの克服は必要不可欠である。有効な治療方法もないのが現状であるため、CAAMRとなりうる患者を未然にもしくは可能な限り早期に発見する診断法の開発が必要である。今回我々が開発した手法によりCAAMRの早期診断が可能になったことで、腎移植の長期成績の最大の問題が解決され長期成績の向上に寄与すると思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (18 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] Addition of Anti-CD40 monoclonal antibody to nonmyeloablative conditioning with belatacept abrogated allograft tolerance despite induction of mixed chimerism.2018

    • Author(s)
      Oura T, Hotta K, Rosales I, Dehnadi A, Kawai K, Lee H, Cosimi AB, Kawai T
    • Journal Title

      Transplantation

      Volume: - Issue: 1 Pages: 168-176

    • DOI

      10.1097/tp.0000000000002417

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term non-human primate renal allograft survival without ongoing immunosuppression in recipients of delayed donor bone marrow transplantation.2018

    • Author(s)
      Hotta K, Oura T, Dehnadi A, Boskovic S, Matsunami M, Rosales I, Smith RN, Colvin RB, Cosimi AB, Kawai T,
    • Journal Title

      Transplantation

      Volume: 102 Issue: 4 Pages: e128-e136

    • DOI

      10.1097/tp.0000000000002078

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【臨床研究報告】小児腎移植における慢性抗体関連型拒絶反応治療後の長期成績の検討.2018

    • Author(s)
      堀田記世彦、岡田宏美、岩見大基、樋口はるか、高田祐輔、篠原信雄
    • Journal Title

      日本小児腎不全学会雑誌

      Volume: 38 Pages: 118-122

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【特集 小児腎不全-移行期医療の管理】12先天性腎尿路異常(CAKUT)管理の現況.2018

    • Author(s)
      堀田記世彦、守屋仁彦、森田 研、岩見大基、篠原信雄
    • Journal Title

      臨床透析

      Volume: 34 Pages: 1149-86

    • Related Report
      2018 Research-status Report
  • [Presentation] A novel immunoresponse monitoring system to predict chronic antibody- mediated rejection in kidney transplant recipients.2020

    • Author(s)
      Naoya Iwahara, Kiyohiko Hotta, Daiki Iwami, Yusuke Takada, Haruka Higuchi, Hajime Sasaki, Tatsu Tanabe, Nobuo Shinohara
    • Organizer
      2020 American Transplant Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎毒性に対してカルシニューリン阻害剤減量、離脱を目的としたエベロリムス導入2019

    • Author(s)
      堀田記世彦、岩見大基、岩原直也、高田祐輔、篠原信雄
    • Organizer
      第52回日本臨床腎移植学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫寛容誘導の臨床応用と将来の展望2019

    • Author(s)
      堀田記世彦、河合達郎
    • Organizer
      第28回日本組織適合性学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血液キメリズムにより誘導された同種腎移植免疫寛容の免疫モニタリング2019

    • Author(s)
      堀田 記世彦、大浦 哲、岩原 直也、岩見 大基、篠原信雄、A. Benedict Cosimi、河合 達郎
    • Organizer
      第55回日本移植学会 総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Retroperitoneoscopic native nephrectomy in renal transplant recipients with autosomal dominant polycystic kidney disease.2019

    • Author(s)
      Hotta K, Iwami D, Furumido J, Morita K, Tanabe T, Mochizuki T, Higuchi H, Iwahara N, Abe T, Shinohara N
    • Organizer
      American urological association annual meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Retroperitoneoscopic native nephrectomy in renal transplant recipients with autosomal dominant polycystic kidney disease.2019

    • Author(s)
      Hotta K, Iwami D, Furumido J, Morita K, Tanabe T, Mochizuki T, Higuchi H, Iwahara N, Abe T, Shinohara N
    • Organizer
      American Transplant Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生体腎移植ドナーの長期予後と腎機能推移の検討2018

    • Author(s)
      堀田記世彦、岩見大基、樋口はるか、篠原信雄
    • Organizer
      第51回日本臨床腎移植学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎移植時における多発性嚢胞腎に対する後腹膜鏡下腎摘術2018

    • Author(s)
      堀田記世彦、岩見大基、古御堂純、森田研、望月端吾、田邉起、佐々木元、広瀬貴行、樋口はるか、高田祐輔、金川匡一、篠原信雄
    • Organizer
      第34回腎移植・血管外科研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎移植における免疫寛容の最前線2018

    • Author(s)
      堀田 記世彦
    • Organizer
      第34回腎移植・血管外科研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生体腎移植ドナーの長期予後と腎機能推移の検討2018

    • Author(s)
      堀田記世彦、岩見大基、樋口はるか、篠原信雄
    • Organizer
      第93回北海道透析療法学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生体腎移植ドナーの長期予後と腎機能推移の検討2018

    • Author(s)
      堀田記世彦、岩見大基、岩原直也、高田祐輔、篠原信雄
    • Organizer
      第404回日本泌尿器科学会北海道地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎移植時における多発性嚢胞腎に対する後腹膜鏡下腎摘術2018

    • Author(s)
      堀田記世彦、岩見大基、古御堂純、森田研、望月端吾、田邉起、佐々木元、広瀬貴行、樋口はるか、高田祐輔、金川匡一、篠原信雄
    • Organizer
      第27回日本腎不全外科研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 常染色体優性多発性嚢胞腎に対する腎移植の自己腎容量に応じた手術手技の選択2018

    • Author(s)
      堀田記世彦、岩見大基、田邉起、岩原直也、古御堂純、森田研、金川 匡一、篠原信雄
    • Organizer
      第54回日本移植学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pre-existing allograft diabetic nephropathy from diabetic donor is reversible after kidney transplantation in non-diabetic recipient.2018

    • Author(s)
      Hotta K, Iwami D, Harada h, Fukasawa Y, Okada H, Higuchi H, Hirose T, Fukuzawa N, Shinohara N
    • Organizer
      American Transplant Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long-term non-human primate renal allograft survival without ongoing immunosuppression in recipients of delayed donor bone marrow transplantation2018

    • Author(s)
      Hotta K, Oura T, Dehnadi A, Matsunami M, Rosales I, Smith RN, Colvin RB, Benichou G, Cosimi AB, Kawai T
    • Organizer
      American Transplant Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] T cell immunomonitoring including donor specific Treg expansion prospectively predicts renal allograft tolerance induced by transient mixed chimerism2018

    • Author(s)
      Hotta K, Oura T, Dehnadi A, Matsunami M, Benichou G, Cosimi AB, Kawai T
    • Organizer
      American Transplant Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long-term Nonhuman Primate Renal Allograft Survival Without Ongoing Immunosuppression in Recipients of Delayed Donor Bone Marrow Transplantation2018

    • Author(s)
      Hotta K, Oura T, Dehnadi A, Matsunami M, Rosales I, Smith RN, Colvin RB, Benichou G, Cosimi AB, Kawai T
    • Organizer
      27th International Congress of The Transplantation Sociaty
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Current topics and next challenge in kidney transplantation- Hokkaido University perspective2018

    • Author(s)
      Hotta K, Iwami D, Shinohara N.
    • Organizer
      Kidney Transplant Asian Summit
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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