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Introduction of novel pharmacodynamics in transplant medicine: Elucidation of the effect of immunosuppressive drugs on B cell

Research Project

Project/Area Number 22590152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKinjo Gakuin University

Principal Investigator

KURATA Yoko  金城学院大学, 薬学部, 助教 (80513928)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Takaaki  名古屋大学, 医学(系)研究科(研究院), 教授 (70314010)
AMIOKA Katsuo  金城学院大学, 薬学部, 教授 (50387594)
KUZUYA Takafumi  名古屋大学, 医学部附属病院, 副部長 (00444406)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsB 細胞 / 薬力学解析 / 免疫抑制薬 / 感受性試験 / 免疫機能モニタリング / B細胞 / 免疫抑制学
Research Abstract

Recently, it has been revealed that the B cells related toanti-donor antibody production have an important role in chronic rejection after organtransplantation. Our attention has been directed towards detailed evaluation of variousimmunosuppressive drugs using pharmacodynamic (PD) analysis of B cell as well as T cell. We attempted to explore the useful combination of PD analysis of B cell andpreviously-established CFSE flow cytometry-based T cell proliferation assay. Obtained results were as follows, (i) calcineurin inhibitor (CNI) suppressedT-independent B cell proliferation through B cell receptor, but not T-dependent B cellproliferation through CD40-40L pathway, (ii) anti-metabolite and mTOR inhibitor (mTOR-I)suppressed T-dependent B cell differentiation, (iii) CNI, antimetabolite and mTOR-I suppressed T cell proliferation, (iv) renal transplant recipients with high sensitivityof CSA to T cell demonstrated high prevalence of viral reactivation, and (v) recipientswith low sens tivity exhibited high incidence of acute T cell mediated rejection.It was suggested that PD analysis of B cell and T cell might make it possible to selectthe optimum drug combination for transplant recipients, leading to individualizedimmunosuppression for prevention of chronic rejection.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (22 results)

  • [Journal Article] Kidney Volume Changes in Patients with Autosomal Dominant Polycystic Kidney Disease after Renal Transplantation2012

    • Author(s)
      Yamamoto T, Watarai Y, Kobayashi T,Matsuda Y, Tsujita M, Hiramitsu T, Nanmoku K, goto N, Katayama A, Tominaga Y, Uchida K.
    • Journal Title

      Transplantation

      Volume: 93 Pages: 794-798

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of cloned pigs expressing human thrombomodulin in endothelial cells2012

    • Author(s)
      Yazaki S, Iwamoto M, Onishi A, Miwa Y,Hashimoto M, Oishi T, Suzuki S, Fuchimoto D, Sembon S, Furusawa T, Liu D, Nagasaka T, Kuzuya T,Ogawa H, Yamamoto K, Iwasaki K, Maruyama S, Kobayashi T.
    • Journal Title

      Xenotransplantation

      Volume: 19 Pages: 82-91

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics and outcomes of renal transplantation in elderly recipients2012

    • Author(s)
      Nanmoku K, Matsuda Y, Yamamoto T,Tsujita M, Hiramitsu T, Goto N, Katayama A, Watarai Y, Kobayashi T, Uchida K.
    • Journal Title

      Transplant Proceedings

      Volume: 44 Pages: 281-3

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy.2012

    • Author(s)
      Yamamoto T, Kawaguchi T, Watarai Y,Tujita M, Hiramitsu T, Nanmoku K, Goto N,Katayama A, Kobayashi T, Uchida K.
    • Journal Title

      Transplant Proceedings

      Volume: 44 Pages: 210-3

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy2012

    • Author(s)
      Yamamoto T, Kawaguchi T, Watarai Y, Tujita M, Hiramitsu T, Nanmoku K, Goto N, Katayama A, Kobayashi T, Uchida K.
    • Journal Title

      Transplant Proc.

      Volume: 44 Issue: 1 Pages: 210-213

    • DOI

      10.1016/j.transproceed.2011.11.048

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics and outcomes of renal transplantation in elderly recipients.2012

    • Author(s)
      Nanmoku K, Kobatashi T, et al.
    • Journal Title

      Transplant Proceedings

      Volume: 44 Issue: 1 Pages: 281-283

    • DOI

      10.1016/j.transproceed.2012.01.006

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative study on signal transduction in endothelial cells after anti-A/B and HLA antibody reaction : implication of accommodation2012

    • Author(s)
      Iwasaki K, Miwa Y, Ogawa H, Iwamoto M, Furusawa T, Onishi A, Kuzuya T, Haneda M, Watarai Y, Uchida K, Kobayashi T.
    • Journal Title

      Transplantation

      Volume: 93 Issue: 4 Pages: 390-397

    • DOI

      10.1097/tp.0b013e3182424df3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipose-derived stromal cells cultured in a low-serum medium, but not bone marrow-derived stromal cells,impede xenoantibody production.2011

    • Author(s)
      Saka Y, Furuhashi K, Katsuno T, Kim H,Ozaki T, Iwasaki K, Haneda M, Sato W,Tsuboi N, Ito Y, Matsuo S, Kobayashi T,Maruyama S.
    • Journal Title

      Xenotransplantation

      Volume: 18 Pages: 196-208

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of Regulatory T Cell-Related Gene Expression in Peripheral Blood After Renal Transplantation.2011

    • Author(s)
      H. Iwase, T. Kobayashi, Y. Kodera, Y.Miwa, T. Kuzuya, K. Iwasaki, M. Haneda, A.Katayama, A. Takeda, K. Morozumi, Y.Watarai, K. Uchida and A. Nakao.
    • Journal Title

      Transplantation

      Volume: 91 Pages: 191-198

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of Regulatory T Cell-Related Gene Expression in Peripheral Blood After Renal Transplantation2011

    • Author(s)
      H.Iwase, T.Kobayashi, et al
    • Journal Title

      Transplantation

      Volume: 91 Issue: 2 Pages: 191-198

    • DOI

      10.1097/tp.0b013e3181ffbab4

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significant Association Between Chronic Antibody-Mediated Rejection and Donor-Specific Antibodies against HLA-DRB rather than DQB in Renal Transplantation.2010

    • Author(s)
      Takaaki Kobayashi,Etsuko Maruya, Misao Niwa, Hiroh Saji, Setsuko Kohara, Akio Katayama, Yoshihiko Watarai, Asami TakedaKazuharu Uchida.
    • Journal Title

      Human Immunology

      Volume: 72 Pages: 11-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of HLA class I antibody-induced antioxidant gene expression for endothelial cell protection against complement attack.2010

    • Author(s)
      Kenta Iwasaki, Yuko Miwa, Masataka Haneda, Kazuharu Uchida, Akimasa Nakao, Takaaki Kobayashi.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 391 Pages: 1210-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Poten t ial value of human thrombomodulin and DAF expression for coagulation control in pig-to-human xenotransplantation2010

    • Author(s)
      Yuko Miwa, Koji Yamamoto, Akira Onishi,Masaki Iwamoto, Satoko Yazaki, Masataka Haneda, Kenta Iwasaki, De.Ge.Liu,Takaharu Nagasaka, Kazuharu Uchida,Akimasa Nakao, Kenji Kadomatsu,Takaaki Kobayashi.
    • Journal Title

      Xenotransplantation

      Volume: 17 Pages: 26-37

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Expansion of donor sources Hurdles of xenotransplantation.2012

    • Author(s)
      Takaaki Kobayashi
    • Organizer
      The 42nd Annual Congress of the Korean Society for Transplantation & The 9th Korea-Japan
    • Place of Presentation
      Transplantation Forum (Korea)
    • Related Report
      2012 Final Research Report
  • [Presentation] Long-Term Outcome in Kidney Transplant Recipients with HTLV-1 Carriers.2012

    • Author(s)
      Goto N, Matsuda Y, Takada M, Yamamoto T,Tsujita M, Hiramitsu T, Nanmoku K, Watarai Y, Katayama A, Kobayashi T, Uchida K.
    • Organizer
      24th International Congress of The Transplantation Society
    • Place of Presentation
      Berlin
    • Related Report
      2012 Final Research Report
  • [Presentation] No Inhibitory Effect of Pre-Transplant Desensitization Treatment with Rituximab or Splenectomy on de Novo HLA Antibody Production in Renal Transplantation2012

    • Author(s)
      Kobayashi T, Yamamoto T, Kuroki K,Hiramitsu T, Tsujita M, Goto N, Nanmoku K,Nagasaka T, Ohtsuka S, Katayama A, WataraiY, Takeda A, Morozumi K, Uchida K
    • Organizer
      24th International Congress of The Transplantation Society
    • Place of Presentation
      Berlin
    • Related Report
      2012 Final Research Report
  • [Presentation] Polycystic Liver and Kidney Volume Changes in Patients with Autosomal Dominant Polycystic Kidney Disease after Renal Transplantation.2012

    • Author(s)
      T. Yamamoto, Y. Watrai, T. Kobayashi, Y.Matsuda, M. Tsujita, T. Hiramitsu, K.Nanmoku, N. Goto, K. Uchida.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] Impacts of Intraoperative Transesophageal Echocardiaography on Hemodynamic Parameter during Operation in Pediatric Renal Transplantation with Less Than 20kg Body Weight.2012

    • Author(s)
      Y. Watarai, Y. Goto, Y. Kuroyanagi, T.Yamada, K. Mori, H. Takasu, T. Yamamoto,M. Tsujita, T. Hiramitsu, N. Goto, K.Nanmoku, T. Ueki, A. Katayama,T.Kobayashi, K. Uchida.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] One Year Post-Transplant but Not Pre-Transplant DSA Levels Predict Subclinical AMR in HLA-Incompatible Renal Transplantation Using Risk-Stratified Desensitization Therapy.2012

    • Author(s)
      S. Yamanaga, Y. Watarai, T. Kobayashi,T. Yamamoto, M. Tsujita, T. Hiramitsu, K.Nanmoku, N. Goto, A. Takeda, K. Morozumi,A. Katayama, K. Uchida.
    • Organizer
      American Transplant Congress2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] Is There an Inhibitory Effect of Pre-Transplant Rituximab Therapy or Splenectomy on De Novo HLA Antibody Production after Renal Transplantation2012

    • Author(s)
      T. Kobayashi, T. Yamamoto, T. Hiramitsu,M. Tsujita, N. Goto, K. Nanmoku, T. Ueki,A. Katayama, A. Takeda, K. Morozumi, Y.Watarai, K. Uchida.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] LongTerm Results of ABO-Incompatible Kidney Transplantation Using Cyclophosphamide and Splenectomy.2012

    • Author(s)
      Y. Watarai, A. Katayama, N. Goto,T.Kobayashi, T. Yamamoto, Y. Matsuda, M.Tsujita, T. Hiramitsu, T. Ueki, K. Nanmoku,A. Takeda, K. Morozumi, K. Uchida.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] Desensitization Protocol UsingIntensified Dose of Mycophenolate Mofetil without Rituximab and Splenectomy for ABO-Incompatible Kidney Transplantation.2012

    • Author(s)
      Y. Watarai, A. Katayama, Y. Matsuda, T.Yamamoto, M. Tsujita, T. Hiramitsu, K.Nanmoku, N. Goto, T. Ueki, A. Takeda, K.Morozumi, T. Kobayashi, K. Uchida.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] Potential Value of Post-Transplant DKB USA Monitoring for Early Diagnosis of Chronic Antibody-Mediated Rejection2011

    • Author(s)
      Takaaki Kobayashi, et al.
    • Organizer
      AMERICAN TRANSPLANT CONGRESS 2011
    • Place of Presentation
      Philadelphia (USA)
    • Year and Date
      2011-05-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional difference between membrane-bound and soluble human thrombomodulin.2011

    • Author(s)
      Yuko Miwa, Satoko Yazaki, Masaki Iwamoto,Kenta Iwasaki, Koji Yamamoto, Masataka Haneda, Akira Onishi, Kazuharu Uchida, Takaaki Kobayashi
    • Organizer
      CTS-IXA 2011 Joint Congress
    • Place of Presentation
      Miami
    • Related Report
      2012 Final Research Report
  • [Presentation] Complement andthrombin block endothelial cellaccommodation.2011

    • Author(s)
      Kenta Iwasaki, Yuko Miwa, MasatakaHaneda, Takaaki Kobayashi
    • Organizer
      CTS-IXA 2011 JointCongress
    • Place of Presentation
      Miami
    • Related Report
      2012 Final Research Report
  • [Presentation] Difference in signal transduction between anti-A/B and anti-HLA antibody binding to endothelial cells.2011

    • Author(s)
      Kenta Iwasaki, Yuko Miwa, Masataka Haneda, Takaaki Kobayashi
    • Organizer
      CTS-IXA 2011 Joint Congress
    • Place of Presentation
      Miami
    • Related Report
      2012 Final Research Report
  • [Presentation] Successful production and breeding of cloned pigs expressing human thrombomodulin in endothelial cells.2011

    • Author(s)
      Masaki Iwamoto, Satoko Yazaki, Akira Onishi, Yuko Miwa, Michiko Hashimoto,Takatsugu Oishi, Shunichi Suzuki,Dai-ichiro Fuchimoto, Shoichiro Sembon,Takaharu Nagasaka, DaGe Liu, Kenta Iwasaki,Masataka Haneda, Koji Yamamoto, Shoichi Maruyama, Takaaki Kobayashi
    • Organizer
      CTS-IXA 2011 Joint Congress
    • Place of Presentation
      Miami
    • Related Report
      2012 Final Research Report
  • [Presentation] The Presence and Strength of IgG3 Subclass Is Associated with Graft Function in DSA-Positive Kidney Transplant Patients.2011

    • Author(s)
      M. Taniguchi, P.I. Terasaki, L.M.Rebellato, T. Kobayashi, P.G.Catrou, K.P. Briley.
    • Organizer
      AMERICAN TRANSPLANT CONGRESS 2011
    • Place of Presentation
      Philadelphia
    • Related Report
      2012 Final Research Report
  • [Presentation] Potential Value of Post-Transplant DRB DSA Monitoring for Early Diagnosis of Chronic Antibody-Mediated Rejection.2011

    • Author(s)
      T. Kobayashi, E.Maruya, M.Taniguchi,M.Niwa, H.Saji, A. Katayama, A.Takeda,Y.Watarai, P.I.Terasaki, K.Uchida.
    • Organizer
      AMERICAN TRANSPLANT CONGRESS 2011
    • Place of Presentation
      Philadelphia
    • Related Report
      2012 Final Research Report
  • [Presentation] Close Relation Between Chronic Antibody Mediated Rejection and Donor Specific Antibody Against Hla Class II DRb, But Not DQb.2010

    • Author(s)
      Takaaki Kobayashi, et al.
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver (Canada)
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pharmacodynamic Evaluation of Cyclosporine in B-Cell.2010

    • Author(s)
      Takafumi Kuzuya, et al.
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver (Canada)
    • Year and Date
      2010-08-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Comparative Study of HLA Antibody Detection Between Elisa and Luminex Assay, and Its Clinical Relevance in Renal Transplantation.2010

    • Author(s)
      Takaaki Kobayashi, et al.
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver (Canada)
    • Year and Date
      2010-08-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] The Implication of AMP-Activated Protein Kinase As A Target To Suppress Lymphocyte Proliferation.2010

    • Author(s)
      Iwasaki K, Hirabayashi A, Kato M,Kuzuya T, Miwa Y, Haneda M, Uchida K, Nakao A, Kobayashi T.
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver
    • Related Report
      2012 Final Research Report
  • [Presentation] Comparative Study of HLA Antibody Detection Between ELISA and Luminex Assay,and Its Clinical Relevance in Renal Transplantation.2010

    • Author(s)
      Kobayashi T, Maruya E, Niwa M, Kohara S,Katayama A, Watarai Y, Saji H, Uchida K
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver
    • Related Report
      2012 Final Research Report
  • [Presentation] Is There an Inhibitory Effect of Pre-Transplant Rituximab Therapy or Splenectomy on De Novo HLA Antibody Production after Renal Transplantation?

    • Author(s)
      Takaaki Kobayashi, et al.
    • Organizer
      American Transplant Congress 2012
    • Place of Presentation
      Boston (USA)
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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