Elucidation of the action mechanism in vivo of AChR-Fc, a novel treatment for myasthenia gravis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07954
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Chiba University
• Principal Investigator: Uzawa Akiyuki 千葉大学, 医学部附属病院, 助教 (10533317)
• Co-Investigator(Kenkyū-buntansha): 桑原 聡 千葉大学, 大学院医学研究院, 教授 (70282481)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 重症筋無力症 / 新規治療 / B細胞 / 融合蛋白 / 動物モデル / 自己抗体 / 自己免疫疾患

Outline of Final Research Achievements

In this project, we aimed to establish a method for identifying pathogenic B cells of MG in order to clarify the action of the fusion protein AChR-Fc, which was developed as a novel therapeutic agent for myasthenia gravis (MG). The expression of pathogenic B cells were analyzed by FACS and ELISPOT using the cells from spleen, bone marrow, and lymph nodes of the MG animal model (EAMG). The proportions of AChR-positive B cells in splenocytes and lymph nodes cells of EAMG rats were higher than those of normal rats. In addition, a large number of spots of IgG2b-positive pathogenic B cells were also confirmed in bone marrow cells of EAMG rats. We were able to identify pathogenic B cells in MG animal model. It will be necessary to analyze changes in pathogenic B cells after therapeutic intervention.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究結果をもとに、今後さらにデータを積み重ねることで、自己抗体産生病原性B細胞の同定方法を完全に確立できれば、患者の血液検体を用いたMG病勢のモニタリングにも応用できる可能性がある。また融合タンパクAChR-Fcが生体内で自己抗体産生病原性B細胞の傷害活性を生じていることを証明できる可能性があり、融合蛋白AChR-FcがMGの有望な新規治療法として臨床応用できることにつながりうる。さらにFc融合技術は他の自己免疫疾患の新規治療としても応用できる可能性があり、社会的意義は大きい。