2022 Fiscal Year Final Research Report

Exploration of antenatal diagnosis and fetal therapy for biliary atresia by liquid biopsy

Research Project

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Project/Area Number	20K21581
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 52:General internal medicine and related fields
Research Institution	Kagoshima University
Principal Investigator	IEIRI Satoshi 鹿児島大学, 医歯学域医学系, 教授 (00363359)
Co-Investigator(Kenkyū-buntansha)	連利博鹿児島大学, 医歯学総合研究科, 客員研究員 (20140444) 山田和歌鹿児島大学, 医歯学総合研究科, 客員研究員 (20457659) 加治建久留米大学, 医学部, 教授 (50315420) 春松敏夫鹿児島大学, 鹿児島大学病院, 特任助教 (70614642) 武藤充鹿児島大学, 医歯学域鹿児島大学病院, 講師 (70404522)
Project Period (FY)	2020-07-30 – 2023-03-31
Keywords	胆道閉鎖症 / 出生前診断 / 肝門部嚢胞 / 臍帯血 / Liquid biopsy / 胎児治療
Outline of Final Research Achievements	Biliary atresia (BA) is a fibroinflammatory cholangiopathy and portal venopathy. It is of unknown etiology and is associated with systemic immune dysregulation, in which the first insult begins before birth. Maternal microchimerism is a naturally occurring phenomenon during fetal life in which maternal alloantigens promote the development of tolerogenic fetal regulatory T-cells in utero. However, maternal cells may alter the fetus's response to self-antigens and trigger an autoimmune response under certain histocompatibility combinations between the mother and the fetus. A recent report on a set of dizygotic discordant twins with BA, one of whose placentae showed villitis of unknown etiology, implies a certain immune-mediated conflict between the fetus with BA and the mother. Maternal chimeric cells persist postnatally for various time spans and can cause cholangitis, which ultimately leads to liver failure.
Free Research Field	小児外科学
Academic Significance and Societal Importance of the Research Achievements	現在本研究課題に関して全国規模の多施設共同研究「出生前診断された胆道閉鎖症患児の胎盤病理および臍帯血中の母親由来細胞に関する多施設共同前向きケース・コントロール研究」を立案し、全国30の周産母子センターが併設された小児外科施設で症例を集積し、解析を行う予定である。また分娩時に得られる臍帯血中に含まれる母親由来細胞のDNA(non-inherited maternal antigen, NIMAのDNA)をrtPCR法により定量してBA 患児と非BA 児とで比較することで、迷入する母親由来細胞の量がBA 発症に及ぼす影響を評価することが出来ると想定している。