Exploring for factors to determine the direction of treatment for myasthenia gravis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07784
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUI Naoko 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (10547954)
• Project Period (FY): 2022-01-04 – 2024-03-31
• Keywords: 重症筋無力症 / 胸腺上皮細胞 / プラズマブラスト / 難治例

Outline of Final Research Achievements

We investigated the factors that determine the pathology and therapeutic response of myasthenia gravis (MG). First, we performed RNA sequence analysis of normal human thymic epithelial cells and confirmed gene expression that is thought to be specific to medullary thymic epithelial cells and cortical thymic epithelial cells in mouse. We have also established an efficient method for isolating thymic epithelial cells and are currently submitting a paper. Next, flow cytometry analysis using peripheral blood mononuclear cells and thymocytes revealed that the expression of CXCR5 in plasmablasts was increased in the thymus of MG patients, and I found that the proportion of intrathymic plasmablasts correlated with the severity of MG. Furthermore, we are proceeding with further verification of whether plasmablasts in the blood can serve as a biomarker in patients with intractable cases.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

MG胸腺を用いたシングルセル解析の報告は数少なく、包括的な検討が十分に行われているとは言い難い。この度、効率的な胸腺上皮細胞（TEC）の単離法を確立したことで、より精度の高いシングルセル解析が可能になると思われる。さらにMG胸腺のcTECやmTECにどのような分子機構が含有されているかを解明することで、MGの病態を明らかにしたい。また治療前のMG胸腺において、プラズマブラストがMGの重症度に関わっていることが明らかとなった。さらに血液中のプラズマブラストは治療後のバイオマーカーとなり得る可能性があり、今後さらなる検証を行うことで、難治MG患者における個別化医療を目指したい。