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Elucidation of pathogenesis of megakaryocyte maturation disorder in idiopathic thrombocytopenic purpura

Research Project

Project/Area Number 16K08973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionKitasato University

Principal Investigator

SATOH TAKASHI  北里大学, 医療衛生学部, 講師 (90407114)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords特発性血小板減少性紫斑病 / 巨核球 / 自己抗体
Outline of Final Research Achievements

To determine the prevalence and pathogenic role of anti-thrombopoietin (TPO) and anti-TPO receptor (TPOR) antibodies in idiopathic thrombocytopenic purpura (ITP) patients. Anti-TPO, anti-TPOR antibodies from 132 patients with ITP and 70 healthy controls were measured by ELISA. To investigate whether anti-TPO, anti-TPOR antibodies inhibited functional interactions between TPO and TPO receptors, we examined ERKs, downstream signals induced by recombinant human TPO (rhTPO) in TPOR-expressing UT-7/TPO. Furthermore, eltrombopag was used instead of rhTPO. Anti-TPO antibodies were detected in 24% of ITP patients and anti-TPOR antibodies were detected in 10% of patients, and none of healthy controls. In half of antibody-positive samples inhibited the phosphorylation of ERK in UT-7/TPO, which might be related to the blocking of rhTPO by anti-TPO or anti-TPOR antibodies. Eltrombopag improved the phosphorylation of ERK in UT-7/TPO in the presence of functional anti-TPO or anti-TPOR antibodies.

Academic Significance and Societal Importance of the Research Achievements

本研究により、ITP患者血漿中からTPOやTPO受容体に対する自己抗体が見出された。さらに、それらの自己抗体の半数例は巨核球系細胞であるUT-7/TPOの下流シグナルに影響を及ぼし、巨核球成熟を抑制する機能的な自己抗体であることが示唆された。これらの結果は、ITPの病態形成機序の解析、治療の作用機序の解明や新たな治療法の開発に繋がる可能性が高いと考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018 2017

All Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Analysis of anti-thrombopoietin receptor antibodyes in patients with immune thrombocyteopenia.2018

    • Author(s)
      Satoh T, Miyazaki K, Horie R
    • Organizer
      The 10th congress of the Asian-Pacific Society on thrombosis and Hemostasis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of anti-thrombopoietin receptor antibodyes in patients with immune thrombocyteopenia.2018

    • Author(s)
      Satoh T, Miyazaki K, Horie R
    • Organizer
      The 23rd Congress of the European Hematology Association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫性血小板減少症(ITP)におけるトロンボポエチン受容体抗体の検出および抗体の機能解析2017

    • Author(s)
      佐藤隆司、宮﨑浩二、堀江良一
    • Organizer
      日本検査血液学会学術大会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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