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Identification of allo-specific antibody responsible for the pathogenesis of neonatal hemochromatosis

Research Project

Project/Area Number 19K08339
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKanazawa University

Principal Investigator

YACHIE AKIHIRO  金沢大学, 附属病院, 特任教授 (40210281)

Co-Investigator(Kenkyū-buntansha) 東馬 智子  金沢大学, 附属病院, 助教 (00377392)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords新生児ヘモクロマトーシス / アロ抗原 / 胎児肝 / 妊娠 / ヘモクロマトーシス / 新生児
Outline of Research at the Start

本研究では、新生児ヘモクロマトーシスの発症の分子機序を明らかにすることを目的とする。とりわけ胎児期に母体から移行する抗原特異的IgG抗体を介して発症するとされる、臓器傷害惹起に関わるアロ抗原を同定すること目指す。これによりハイリスク妊婦のスクリーニング、胎児期早期の確定診断、適切な治療介入のための新たなバイオマーカーの提案などが可能となる。本研究により標的となる胎児抗原が明らかとされ、母体中の抗体を検出する手法が確立されることにより高い治療効果を示すとされ、医師主導治験が行われている母体への高用量免疫グロブリン投与についても、理論的な裏付けがなされ、治療の一般化が促進されることが期待される。

Outline of Final Research Achievements

Neonatal hemochromatosis is a fatal disease of fetus and infants with severe liver injury and systemic iron deposition. There is indirect evidence that maternally-derived antibody against fetal organ is responsible for the disease, although the exact antigen has not been determined to date.
In this study, protein-active array method was utilized to find candidate antigens of NH. Several proteins have been found as a possible target for the NH allo-reactive antibody. These targets are among proteins expressed specifically within fetal liver tissue. Further study is undergoing to prove the specificity of this antigen and to clarify the direct relationship between NH pathology and antibody directed against these antigens.

Academic Significance and Societal Importance of the Research Achievements

本研究では、新生児ヘモクロマトーシスの発症の分子機序を明らかにすることを目的とする。とりわけ、胎児期に母体から移行する抗原特異的IgG抗体を介して発症するとされる、臓器傷害の惹起に関わるアロ抗原を同定すること目指す。これにより、ハイリスク妊婦のスクリーニング、胎児期早期の確定診断、適切な治療介入のための新たなバイオマーカーの提案などが可能となる。
現在、高い治療効果を示すとされ、医師主導治験が行われている母体への高用量免疫グロブリン投与についても、理論的な裏付けがなされ、治療の一般化が促進されることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results)

  • [Journal Article] Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models2021

    • Author(s)
      Yachie A
    • Journal Title

      INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

      Volume: 22 Issue: 4 Pages: 1514-1514

    • DOI

      10.3390/ijms22041514

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis during tocilizumab therapy.2020

    • Author(s)
      Irabu H, Shimizu M, Kaneko S, Inoue N, Mizuta M, Nakagishi Y, Yachie A.
    • Journal Title

      Pediatric Research

      Volume: in press Issue: 6 Pages: 934-939

    • DOI

      10.1038/s41390-020-0843-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.2019

    • Author(s)
      Takakura M, Shimizu M, Irabu H, Sakumura N, Inoue N, Mizuta M, Nakagishi Y, Yachie A.
    • Journal Title

      Clinical Immunology

      Volume: in press Pages: 108252-108252

    • DOI

      10.1016/j.clim.2019.108252

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage activation syndrome in neonates born to mothers with adult-onset Still's disease: Perinatal effect of maternal IL-18.2019

    • Author(s)
      Shimizu M, Kizawa T, Kato R, Suzuki T, Yachie A.
    • Journal Title

      Clin Immunol

      Volume: 207 Pages: 36-39

    • DOI

      10.1016/j.clim.2019.07.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] C/EBPε ΔRS derived from a neutrophil-specific granule deficiency patient interacts with HDAC1 and its dysfunction is restored by trichostatin A.2019

    • Author(s)
      Muraoka M, Akagi T, Ueda A, Wada T, Koeffler HP, Yokota T, Yachie A.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 516 Issue: 1 Pages: 293-299

    • DOI

      10.1016/j.bbrc.2019.06.130

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of serum CXCL9 levels as a biomarker for systemic juvenile idiopathic arthritis associated macrophage activation syndrome.2019

    • Author(s)
      Mizuta M, Shimizu M, Inoue N, Nakagishi Y, Yachie A.
    • Journal Title

      Cytokine

      Volume: 119 Pages: 182-187

    • DOI

      10.1016/j.cyto.2019.03.018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed

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Published: 2019-04-18   Modified: 2023-01-30  

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