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Maternal DNA in the peripheral blood of patients with biliary atresia affect the prognosis

Research Project

Project/Area Number 17K11514
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionKagoshima University

Principal Investigator

MURAJI Toshihiro  鹿児島大学, 医歯学総合研究科, 客員研究員 (20140444)

Co-Investigator(Kenkyū-buntansha) 家入 里志  鹿児島大学, 医歯学域医学系, 教授 (00363359)
大西 峻  鹿児島大学, 医歯学総合研究科, 客員研究員 (10614638)
諸冨 嘉樹  大阪市立大学, 大学院医学研究科, 講師 (20263907)
増本 幸二  筑波大学, 医学医療系, 教授 (20343329)
原 博満  鹿児島大学, 医歯学域医学系, 教授 (20392079)
加治 建  鹿児島大学, 鹿児島大学病院, 特任教授 (50315420)
武藤 充  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (70404522)
桝屋 隆太  鹿児島大学, 医学部・歯学部附属病院, その他 (90448572)
堀池 正樹  大阪市立大学, 大学院医学研究科, 登録医 (30464621)
古川 泰三  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20515291)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胆道閉鎖症 / 母親キメリズム / 母親寛容 / 混合リンパ球試験 / 母親由来キメラ細胞
Outline of Final Research Achievements

A mixed lymphocyte test between mother and infant of 7 patients was performed.
In 6 cases, the mother's response to the child's antigen stimulation was variously smaller than the response by the third party.One patient with a favorable prognosis did not have tolerance formation and the patient had a strong reaction to the mother, suggesting that she could eliminate effector lymphocytes from Th1. Further evaluation should confirm the phenotype of the responding cells and whether or not maternal cells are present in the peripheral blood of the child.In two cases with different prognosis, there was a group in which the mother's reaction to the patient's antigen stimulation was equivalent to that of a third party.The difference is that the mother's antigen stimulation response of the patient was as strong as that of a third party in the case of poor prognosis.In the future, it is necessary to look at the phenotype of cells that differentiate and proliferate upon antigen stimulation.

Academic Significance and Societal Importance of the Research Achievements

胆道閉鎖症は発症メカニズムが解明されていない疾患である。胆道閉鎖症の原因とMaternal microchimerismの関連を明らかにし、病因の解明に寄与すると考えられる。Maternal microchimerismと胆道閉鎖症の疾患メカニズムとの関連が明らかになることで、胎生期からの診断と予防方法の解明、また新たな治療の開発、ひいては肝移植に依らない自己肝生存率の改善に大いに寄与することが期待できる。
また、患者の肝生検組織中の母親細胞の肝内分布を解析することにもつながり、最終的に母親細胞が組織障害を惹起することを明らかにし、予防法解明につなげることが期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Cecal diverticulitis: Two pediatric cases2019

    • Author(s)
      Yano Keisuke、Muraji Toshihiro、Hijikuro Kaoru、Shigeta Koichiro、Ieiri Satoshi
    • Journal Title

      Pediatrics International

      Volume: 61 Issue: 9 Pages: 931-933

    • DOI

      10.1111/ped.13940

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphometrical analyses on narrowing of portal veins and thickening of hepatic arteries in the liver of biliary atresia2019

    • Author(s)
      Masuya R, Muraji T, Ohtani H, Mukai M, Onishi S, Harumatsu T, Yamada K, Yamada W, Kawano T, Machigashira S, Nakame K, Kaji T, Ieiri S
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 5 Pages: 529-537

    • DOI

      10.1007/s00383-019-04459-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histological significance of hepatitis‐like findings in biliary atresia: An analysis of 34 Japanese cases2019

    • Author(s)
      Suda Kazuto、Muraji Toshihiro、Ohtani Haruo、Aiyoshi Tsubasa、Sasaki Takato、Toma Miki、Yanai Toshihiro
    • Journal Title

      Pediatrics International

      Volume: 61 Issue: 4 Pages: 364-368

    • DOI

      10.1111/ped.13816

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic Factors for Native Liver Survival in Patients With Biliary Atresia After Kasai Portoenterostomy2018

    • Author(s)
      桝屋 隆太、家入 里志、連 利博、中目 和彦、川野 孝文、春松 敏夫、山田 和歌、町頭 成郎、向井 基、加治 建
    • Journal Title

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 54 Issue: 7 Pages: 1324-1331

    • DOI

      10.11164/jjsps.54.7_1324

    • NAID

      130007535913

    • ISSN
      0288-609X, 2187-4247
    • Year and Date
      2018-12-20
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ethnic variation in the incidence of biliary atresia correlates with the frequency of the most prevalent haplotype in its population2018

    • Author(s)
      Muraji Toshihiro、Tanaka Hidenori、Ieiri Satoshi
    • Journal Title

      Human Immunology

      Volume: 79 Issue: 9 Pages: 668-671

    • DOI

      10.1016/j.humimm.2018.07.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictive factors affecting the prognosis and late complications of 73 consecutive cases of esophageal atresia at 2 centers2018

    • Author(s)
      Masuya Ryuta、Kaji Tatsuru、Mukai Motoi、Nakame Kazuhiko、Kawano Takafumi、Machigashira Seiro、Yamada Waka、Yamada Koji、Onishi Shun、Yano Keisuke、Moriguchi Tomoe、Sugita Koshiro、Kawano Masato、Noguchi Hiroyuki、Suzuhigashi Masaya、Muto Mitsuru、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 34 Issue: 10 Pages: 1027-1033

    • DOI

      10.1007/s00383-018-4326-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GvHD仮説からみた成因と発症時期2018

    • Author(s)
      連 利博, 桝屋隆太、向井 基、家入里志
    • Journal Title

      小児外科

      Volume: 50 Pages: 16-20

    • Related Report
      2018 Research-status Report
  • [Journal Article] 特集 胆道閉鎖症アップデート:GvHD仮説からみた成因と発症時期2018

    • Author(s)
      連 利博、桝屋隆太、向井 基、家入里志
    • Journal Title

      小児外科

      Volume: 50 Pages: 16-20

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The accumulation of regulatory T cells in the hepatic hilar lymph nodes in biliary atresia2017

    • Author(s)
      Sakamoto Naoya、Muraji Toshihiro、Ohtani Haruo、Masumoto Kouji
    • Journal Title

      Surgery Today

      Volume: 47 Issue: 10 Pages: 1282-1286

    • DOI

      10.1007/s00595-017-1502-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unique manifestations of biliary atresia provide new immunological insight into its etiopathogenesis2017

    • Author(s)
      Muraji Toshihiro、Ohtani Haruo、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 12 Pages: 1249-1253

    • DOI

      10.1007/s00383-017-4155-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The ethnic variation in the incidence of biliary atresia.2019

    • Author(s)
      Muraji T, Masuya R, Harumatsu T, Ieiri S
    • Organizer
      The 8th Symposium on Biliary Atresia and Pediatric Liver Transplantation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胆道閉鎖症のマススクリーニング2019

    • Author(s)
      連 利博
    • Organizer
      第46回 マススクリーニング学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Morphometrical analyses on the narrowing of portal veins and thickening of media of hepatic arteries in the liver of biliary atresia.2018

    • Author(s)
      Masuya R, Muraji T, Ohtani H, Mukai M, Onishi S, Harumatsu T, Yamada K, Yamada W, Kawano T, Machigashira S, Nakame K, Kaji T, Ieiri S
    • Organizer
      The 25th Congress of the Asian Association of Pediatric Surgeons
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The physical growth and social prognosis of esophageal atresia patients who reach 15 years of age or older: The long-term outcomes at a single institution2018

    • Author(s)
      Masuya R, Kaji T, Murakami M, Yano K, Baba T, Harumatsu T, Onishi S, Yamada K, Yamada W, Kawano T, Machigashira S, Mukai M, Nakame K, Mukai M, Ieiri S
    • Organizer
      The 25th Congress of the Asian Association of Pediatric Surgeons
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Morphometrical analyses on narrowing of portal veins and thickening of hepatic arteries in liver of biliary atresia.2018

    • Author(s)
      Masuya R, Muraji T, Ohtani H, Mukai M, Yano K, Kawano M, Onishi S, Yamada K, Yamada W, Kawano T, Machigashira S, Nakame K, Kaji T, Ieiri S
    • Organizer
      The 51st Annual Scientific Meeting of the Pacific Association of Pediatric Surgeons
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胆道閉鎖症の葛西手術時肝生検検体における門脈枝および肝動脈枝の形態計測学的検討2018

    • Author(s)
      桝屋隆太, 連 利博, 大谷明夫, 矢野圭輔, 大西 峻, 山田耕嗣, 山田和歌, 川野孝文,中目和彦, 向井 基, 加治 建, 家入里志
    • Organizer
      第45回日本胆道閉鎖症研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 定量的PCRを用いた母親由来キメラ細胞の定量および母児間混合リンパ球培養との比較検討を行った胆道閉鎖症患児の1例2018

    • Author(s)
      桝屋隆太, 連 利博, 矢野圭輔, 大西 峻, 山田耕嗣, 山田和歌, 川野孝文, 中目和彦,向井 基, 加治 建, Sami B Kanaan, J Lee Nelson, 家入里志
    • Organizer
      第45回日本胆道閉鎖症研究会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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