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A multifaceted approach to HLA antibody-producing B cells for donor-specific antibody (DSA) regulation

Research Project

Project/Area Number 18K08584
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionAichi Medical University

Principal Investigator

NODA Takayuki  愛知医科大学, その他部局等, 薬剤師 (50817088)

Co-Investigator(Kenkyū-buntansha) 小林 孝彰  愛知医科大学, 医学部, 教授 (70314010)
岩崎 研太  愛知医科大学, 医学部, 准教授 (10508881)
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords臓器移植 / DSA / ヒト化マウス / バイオマーカー / B細胞培養 / B細胞 / HLA抗体 / 腎移植
Outline of Final Research Achievements

The aim of this study is to establish a method for monitoring donor-specific anti-HLA (DSA) antibodies after transplantation that enables early diagnosis of chronic rejection. Detection of antibodies in the culture system was clearer than in serum. This method was found to be more advantageous for early diagnosis in some patients than in serum. We started to create a humanized mouse model of HLA antibody production to analyze DSA-producing B cells in the human body. However, model mice have yet to be established due to the lack of stability in antibody production.

Academic Significance and Societal Importance of the Research Achievements

臓器移植における拒絶反応は、主にT細胞が関連する細胞性の拒絶反応と、B細胞が関連する抗体関連型拒絶反応(Antibody-Mediated Rejection: ABMR)の二つが存在する。免疫抑制剤の進歩により細胞性拒絶反応の制御がほぼ可能となった現在、ABMRの克服が臨床的に重要な課題となっている。中でもde novo のドナー特異的抗HLA抗体(Donor Specific HLA Antibody: DSA)産生を引き金とする慢性抗体関連型拒絶反応(Chronic ABMR: CAMR)に対する有効な予防法・治療法は確立されていない。

Report

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

    (7 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (6 results)

  • [Journal Article] Increased CD40L+PD-1+ follicular helper T cells (Tfh) as a biomarker for predicting calcineurin inhibitor sensitivity against Tfh-mediated B-cell activation/antibody production after kidney transplantation2018

    • Author(s)
      Iwasaki Kenta、Kitahata Nana、Hiramitsu Takahisa、Yamamoto Takayuki、Noda Takayuki、Okada Manabu、Narumi Shunji、Watarai Yoshihiko、Miwa Yuko、Uchida Kazuharu、Matsuoka Yutaka、Horimi Kosei、Kobayashi Takaaki
    • Journal Title

      International Immunology

      Volume: 30 Issue: 8 Pages: 345-355

    • DOI

      10.1093/intimm/dxy039

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト化マウスを用いたドナー特異的抗体(DSA)産生モデルの構築2019

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、小林孝彰
    • Organizer
      第3回東海北陸HLA研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] ドナー特異的抗体(DSA)検出に向けたヒト化マウスの作製2019

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、小林孝彰
    • Organizer
      第28回日本組織適合性学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト化マウスを用いたドナー特異的抗体(DSA)産生モデルの樹立2019

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、小林孝彰
    • Organizer
      第55回日本移植学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ドナー特異的抗体(DSA)検出を目指したヒト化マウスの作製2019

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、小林孝彰
    • Organizer
      第46回日本臓器保存生物医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] DSA産生B細胞の機能解析に向けたin vitro培養系の確立とヒト化マウスの作製2018

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、相原祐子、河野あゆみ、斎藤寛子、小林孝彰
    • Organizer
      第27回組織適合性学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] DSA産生B細胞の機能解析のためのin vitro培養系とヒト化マウスの作製2018

    • Author(s)
      野田貴幸、岩崎研太、三輪祐子、相原祐子、河野あゆみ、斎藤寛子、小林孝彰
    • Organizer
      第54回移植学会総会
    • Related Report
      2018 Research-status Report

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

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