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

移植医学新药效学介绍：阐明免疫抑制药物对 B 细胞的影响

• 批准号: 22590152
• 负责人: KURATA Yoko
• 金额: $ 2.5万
• 依托单位: Kinjo Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590152/
• 关键词: B 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

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.

最近，研究发现与抗供体抗体产生相关的B细胞在器官移植后的慢性排斥反应中发挥重要作用。我们的注意力集中在使用 B 细胞和 T 细胞的药效 (PD) 分析来详细评估各种免疫抑制药物。我们试图探索 B 细胞的 PD 分析与先前建立的基于 CFSE 流式细胞术的 T 细胞增殖测定的有用组合。获得的结果如下，（i）钙调磷酸酶抑制剂（CNI）通过B细胞受体抑制T非依赖性B细胞增殖，但不通过CD40-40L途径抑制T依赖性B细胞增殖，（ii）抗代谢物和mTOR抑制剂（mTOR-I）抑制T依赖性B细胞分化，（iii）CNI、抗代谢物和 mTOR-I 抑制 T 细胞增殖，(iv) CSA 对 T 细胞高度敏感的肾移植受者表现出病毒再激活的高发生率，(v) 敏感性低的受者表现出急性 T 细胞介导的排斥反应的高发生率。这表明 B 细胞和 T 细胞的 PD 分析可能使为移植受者选择最佳药物组合成为可能，从而导致 个体化免疫抑制预防慢性排斥反应。

项目成果

The Presence and Strength of IgG3 Subclass Is Associated with Graft Function in DSA-Positive Kidney Transplant Patients.

IgG3 亚类的存在和强度与 DSA 阳性肾移植患者的移植物功能相关。

• 发表时间: 2011
• 作者: M. Taniguchi;P.I. Terasaki;L.M.Rebellato;T. Kobayashi;P.G.Catrou;K.P. Briley.
• 通讯作者: K.P. Briley.

Kidney Volume Changes in Patients With Autosomal Dominant Polycystic Kidney Disease After Renal Transplantation

• DOI: 10.1097/tp.0b013e318246f910
• 发表时间: 2012-04-27
• 期刊: TRANSPLANTATION
• 影响因子: 6.2
• 作者: Yamamoto, Takayuki;Watarai, Yoshihiko;Uchida, Kazuharu
• 通讯作者: Uchida, Kazuharu

Long-Term Outcome in Kidney Transplant Recipients with HTLV-1 Carriers.

HTLV-1 携带者肾移植受者的长期结果。

• 发表时间: 2012
• 作者: Goto N;Matsuda Y;Takada M;Yamamoto T,Tsujita M;Hiramitsu T;Nanmoku K;Watarai Y;Katayama A;Kobayashi T;Uchida K.
• 通讯作者: Uchida K.

The Implication of AMP-Activated Protein Kinase As A Target To Suppress Lymphocyte Proliferation.

AMP 激活蛋白激酶作为抑制淋巴细胞增殖的靶标的意义。

• 发表时间: 2010
• 作者: Iwasaki K;Kobayashi T;et al.
• 通讯作者: et al.

Production of cloned pigs expressing human thrombomodulin in endothelial cells

• DOI: 10.1111/j.1399-3089.2012.00696.x
• 发表时间: 2012-03
• 期刊: Xenotransplantation
• 影响因子: 3.9
• 作者: S. Yazaki;M. Iwamoto;A. Onishi;Y. Miwa;Michiko Hashimoto;T. Oishi;Shun'ichi Suzuki;D. Fuchimoto;S. Sembon;T. Furusawa;Dage Liu;T. Nagasaka;T. Kuzuya;H. Ogawa;Koji Yamamoto;Kenta Iwasaki;M. Haneda;S. Maruyama;Takaaki Kobayashi