A Multicenter Prospective Case-Control Study on Etiopathogenetic Role of Maternal Cells in Biliary Atresia on Disease Control using Cord-Blood Analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• 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) ; 齋藤 滋 富山大学, 大学本部, 学長 (30175351) ; 津田 さやか 富山大学, 学術研究部医学系, 助教 (60839075) ; 春松 敏夫 鹿児島大学, 鹿児島大学病院, 特任助教 (70614642)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胆道閉鎖症 / 母親マイクロキメリズム / 混合リンパ球培養

Outline of Final Research Achievements

Biliary atresia (BA) is an immune-mediated inflammatory bile duct disease of unknown etiology in newborns and infants, ultimately requiring liver transplantation in half of the patients. As maternal cells are found in the significant number in the liver of patients with BA, we proceeded our research based on the hypothesis that materno-fetal immune dysregulation causes bile duct damage. Mixed lymphocyte reaction between the 9 patients with BA and their mothers disclosed upregulation of immune-interaction in all. Among 12 patients with BA, 328 maternal cells out of 1,000,000 host cells in average were detected in the peripheral blood of 7 patients during their follow-up, of whom five patients showed poor prognosis. This suggests that circulating maternal chimeric lymphocytes might have some role in its etiopathogenesis.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

本疾患を有する患児の肝臓に母親由来細胞が多く存在することと本疾患メカニズムとの関連が明らかになれば、発症の予測が可能となり、胎生期からの診断さらには予防方法の開拓また新たな治療の開発、すなわち臓器提供者を必要とする肝移植に依らない自己肝で生存できる可能性も期待できる。