Elucidation of pathogenesis of megakaryocyte maturation disorder in idiopathic thrombocytopenic purpura

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08973
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kitasato 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
• 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.

Free Research Field

血液検査学

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。