Construction of Appropriate Indicators for Evaluating Humoral Immune Recovery After Allogeneic Hematopoietic Cell Transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17406
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Kimura Shun-ichi 自治医科大学, 医学部, 准教授 (70623031)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: IgG / B細胞受容体レパトア / 肺炎球菌 / インフルエンザ桿菌 / 莢膜を有する細菌 / IGHV / IGHV-CDR3 / 液性免疫

Outline of Final Research Achievements

The objective was to clarify the features of IgG B-cell receptor (BCR) repertoire diversity among patients with and without infections caused by encapsulated bacteria such as S. pneumoniae and H. influenzae after allogeneic HCT. The frequency of the usage of IGHV3-11 (P = 0.012) and IGHV4-59 (P = 0.04) were significantly lower in Pt. The length of amino acids (AA) in IGHV-CDR3 of all clones seemed to be symmetrically distributed, and the most frequently observed AA length was 16 (13.7%) followed by 17 (11.2%). In Rep, 17AA (17.7%) and 21AA (16.7%) were mainly used while the frequency of 16AA was low (4.4%). Apparently, the decreased diversity in the AA motifs in 17AA and 21AA in Rep was observed. The decreased usage of IGHV3-11 and IGHV4-59, and the change in frequency of AA length and its decreased diversity in IGVH-CDR3 might be associated with the increased vulnerability to encapsulated bacteria.

Free Research Field

造血細胞移植

Academic Significance and Societal Importance of the Research Achievements

同種移植後の液性免疫の回復と感染性合併症、特に液性免疫不全がリスクとなる肺炎球菌、インフルエンザ桿菌などの莢膜を有する細菌との関連について、B細胞受容体レパトアを解析して検証した。本研究の結果が、これらの莢膜を有する細菌に対する易感染性のメカニズムを明らかにする重要なデータとなるとともに、この研究内容をさらに発展させていくことで、これらの感染症に有効な特定の免疫グロブリン製剤の製造やワクチンの開発などにつながる可能性がある。さらに同種移植後の液性免疫の状態を正確に評価する指標の構築にもつながる結果になると考えられる。