Elucidation of myasthenia gravis thymus pathology and development of new treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23946
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• 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), 特任助教 (10547954)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 重症筋無力症 / 胸腺 / B細胞 / プラズマブラスト

Outline of Final Research Achievements

We investigated intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 non-thymoma MG patients, and 11 thymoma MG patients were subjected to flow cytometry analysis of B cell subsets and inflammatory cytokines. Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated MG patients were also analyzed. Immunological values were compared, and correlations between relevant values and clinical parameters were evaluated. We found increased frequencies of circulating as well as intrathymic plasmablasts in MG patients. We postulate the migration of peripheral B cells into the thymus, whereby activated intrathymic plasmablasts endow pathogenic capacity in MG. We are also establishing a process for the purification of human thymic epithelial cells.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

本研究によって、MG胸腺における新たな免疫学的な背景が明らかとなった。MG患者ではステロイド投与後も、胸腺摘出術がプラズマブラストの減少を通じて症状の安定に寄与する可能性がある。今後、プラズマブラストが治療反応性を予測するバイオマーカーとなり得るか、治療抵抗例におけるプラズマブラストの解析を進め、難治例に対する対策へと発展させたい。