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

• Project/Area Number: 17K11514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Kagoshima 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: ¥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。

Research Products

• [Journal Article] Cecal diverticulitis: Two pediatric cases (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Morphometrical analyses on narrowing of portal veins and thickening of hepatic arteries in the liver of biliary atresia (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Histological significance of hepatitis‐like findings in biliary atresia: An analysis of 34 Japanese cases (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Factors for Native Liver Survival in Patients With Biliary Atresia After Kasai Portoenterostomy (2018)
  • 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
  • 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 population (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Predictive factors affecting the prognosis and late complications of 73 consecutive cases of esophageal atresia at 2 centers (2018)
  • 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
  • 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
• [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
  • Peer Reviewed
• [Journal Article] The accumulation of regulatory T cells in the hepatic hilar lymph nodes in biliary atresia (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Unique manifestations of biliary atresia provide new immunological insight into its etiopathogenesis (2017)
  • 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
  • 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
  • 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
• [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
  • 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 institution (2018)
  • 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
  • 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
  • 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
• [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