Biochemical characteristics of erythrocytes in extremely preterm infants and identification of loci conferring susceptibility to prolonged severe hyperbilirubinemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nihon University
• Principal Investigator: MORIOKA Ichiro 日本大学, 医学部, 教授 (80437467)
• Co-Investigator(Kenkyū-buntansha): 菅野 仁 東京女子医科大学, 医学部, 特任教授 (70221207) ; 谷ヶ崎 博 日本大学, 医学部, 准教授 (90378141)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 赤血球 / 遷延性重症黄疸 / 臍帯血

Outline of Final Research Achievements

Values of flow cytometric osmotic fragility (FCM-OF) and Eosin 5'-Maleimide (EMA) binding capacity of erythrocytes in cord blood (CB) were measured to generate reference values and compared with those of erythrocytes in adult blood (AP). To identify genes associated with prolonged severe hyperbilirubinemia, a next-generation sequencing panel of 63 target genes was evaluated in infants with congenital hemolytic anemia. There were significant differences in FCM-OF and EMA measurements between CB and AP. The reference values for CB were established. Next-generation sequencing analysis revealed that among children with spontaneous remission of hemolytic anemia by 1 year of age, there were those with variant of uncertain significance in PIEZO1.

Free Research Field

新生児医学

Academic Significance and Societal Importance of the Research Achievements

古くから「特発性新生児黄疸」という疾患名が定着し、新生児の黄疸は原因が不明であることが一般的になっている。また、赤血球関連特殊検査の多くの項目に新生児の基準値がなかった。本研究で初めて、臍帯血の赤血球関連特殊検査のflow cytometric osmotic fragility（FCM-OF）およびEosin 5’-Maleimide（EMA）結合能の基準値を作成できた。PIEZO1の変異が一過性の溶血により重症の新生児黄疸を引き起こす可能性があることを明らかにし、原因不明だった重症新生児黄疸の原因や病態解明ができた。