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造血細胞移植に関わる新たなアロ免疫認識機構の解明

Publicly Offered Research

Project AreaCreation, function and structure of neo-self
Project/Area Number 17H05797
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of the Ryukyus

Principal Investigator

森島 聡子  琉球大学, 医学(系)研究科(研究院), 准教授 (40463195)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
KeywordsHLA / 同種造血幹細胞移植 / アロ免疫 / 造血細胞移植学 / 免疫学
Outline of Annual Research Achievements

本研究は、ヒトのアロ免疫認識機構により生じる移植免疫反応へのHLA遺伝子領域の関与を詳細に解析し、新たなアロ免疫機構を明らかにすることを目的としている。
昨年度は、HLA-DPB1の非翻訳領域を含む全領域ゲノム情報に基づき作成した系統樹と非血縁者間骨髄移植症例の大規模免疫遺伝データべースを用いて、非翻訳領域に急性GVHDの新たな発症機構が存在し、従来のT細胞エピトープに基づくHLAアリルとその適合度により生じるGVHD発症機構とは異なることを世界に先駆けて明らかにし、論文化した。本研究期間においては、他のHLA遺伝子の分子系統解析による群分けがHLA-DPB1遺伝子と同様なメカニズムで、移植後のアロ免疫反応によって起こる臨床病態に影響するかを探るために、HLA-A、-B、-C、-DRB1、-DQB1遺伝子全領域を区分化して系統樹解析を開始した。
さらに、白血病患者の同種造血幹細胞移植を施行され再発した例でアロ免疫からの回避機構におけるHLAの意義を検索するため、患者の初診時、化学療法後再発時、移植後再発時など経時的に採取保存された検体でのHLA解析を開始し、データを構築中である。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (9 results)

All 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Reference Grade Characterization of Polymorphisms in Full-Length HLA Class I and II Genes With Short-Read Sequencing on the ION PGM System and Long-Reads Generated by Single Molecule, Real-Time Sequencing on the PacBio Platform.2018

    • Author(s)
      Suzuki S, Ranade S, Osaki K, Ito S, Shigenari A, Ohnuki Y, Oka A, Masuya A, Harting J, Baybayan P, Kitazume M, Sunaga J, Morishima S, Morishima Y, Inoko H, Kulski JK, Shiina T.
    • Journal Title

      Front Immunol.

      Volume: 9 Pages: 2294-2294

    • DOI

      10.3389/fimmu.2018.02294

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.2018

    • Author(s)
      Tamaki K, Morishima S, Nomura S, Nishi Y, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Taira N, Tomoyose T, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Fukushima T, Masuzaki H.
    • Journal Title

      Cancer Sci.

      Volume: 109 Issue: 7 Pages: 2286-2293

    • DOI

      10.1111/cas.13641

    • NAID

      120006937800

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation.2018

    • Author(s)
      Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K, Azuma F, Yabe T, Satake M, Kato S, Kodera Y, Sasazuki T, Morishima Y
    • Journal Title

      Blood

      Volume: 131(7) Issue: 7 Pages: 808-817

    • DOI

      10.1182/blood-2017-08-801449

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Risk of HLA Homozygous Cord Blood Transplantation: Implications for Induced Pluripotent Stem Cell Banking and Transplantation.2018

    • Author(s)
      Morishima Y, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Nakajima K, Morishima S, Satake M, Takanashi M, Yabe T
    • Journal Title

      Stem Cells Transl Med.

      Volume: 7(2) Issue: 2 Pages: 173-179

    • DOI

      10.1002/sctm.17-0169

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLA-DPB1 mismatch induces a graft-versus-leukemia (GVL) effect without severe acute GVHD after single-unit umbilical cord blood transplantation2018

    • Author(s)
      Yabe T, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Morishima S, Satake M, Takanashi M, Nakajima K, Morishima Y
    • Journal Title

      Leukemia

      Volume: 168-175 Issue: 1 Pages: 168-175

    • DOI

      10.1038/leu.2017.202

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 造血細胞移植に関わる新たなアロ免疫認識機構の解明2018

    • Author(s)
      森島 聡子
    • Organizer
      第27回日本組織適合性学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非血縁者間骨髄移植における日本人の高頻度HLAハプロタイプ (HP-P2)の急性GVHD抑制効果2018

    • Author(s)
      森島聡子、東史啓、屋部登志雄、柏瀬貢一、椎名隆、加藤俊一、小寺良尚、笹月健彦、森島泰雄
    • Organizer
      第40回日本造血細胞移植学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Impact of mismatched HLA on graft-versus-host disease in unrelated stem cell transplantation2017

    • Author(s)
      森島聡子
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] JMDP HLA-DP study update -Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation-2017

    • Author(s)
      Satoko Morishima
    • Organizer
      The 17th International & Immunogenetics Workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2019-12-27  

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