Elucidation of angiopathy mechanism and development of therapeutic methods in chronic active Epstein-Barr virus disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16410
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Ohashi Ayaka 聖マリアンナ医科大学, 医学部, 助教 (60844371)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 慢性活動性Epstein-Barrウイルス病 / CAEBV / 血管病変 / IL-1β / 血管内皮細胞 / 凝固

Outline of Final Research Achievements

Supernatants from chronic active Epstein-Barr virus disease (CAEBV) cell lines affected the expression of coagulation-related factors in vascular endothelial cell lines and activated coagulation. Cytokine array was performed using CAEBV patients' plasma to identify the causative factors. IL-1β was highly expressed in the plasma of patients with vascular lesions and not in patients without them. IL-1β inhibited cell proliferation and enhanced coagulation activity of vascular endothelial cells. IL-1β was found to contribute to the development of vascular lesions associated with CAEBV. Furthermore, we also clarified the correlation between IFN-γ and hemophagocytic lymphohistiocytosis.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

CAEBV患者の25%が発症する血管病変は、臓器傷害やTMA発症などに関与し、唯一の根治療法である造血幹細胞移植の移植成績を低下させ、予後を悪化させる極めて重篤な病態である。IL-1βが血管病変を合併したCAEBV患者の血漿中でのみ認められたことは、IL-1βがCAEBVで高率に合併する血管病変の発症に関与し、治療標的となることを示唆した。IFN-γなど他の液性因子とCAEBV病態との関連も見出している。本研究成果は、CAEBVに併発する血管病変だけではなく、HLH等の病変の発症や病態解明に寄与すると共に、IL-1β等液性因子を標的とした治療法やバイオマーカーの開発に貢献し得る。