EBV reactivation-induced autoantibody production and management of Graves' disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08694
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tottori University
• Principal Investigator: NAGATA Keiko 鳥取大学, 医学部, 講師 (50304209)
• Co-Investigator(Kenkyū-buntansha): 林 一彦 鳥取大学, 医学部, 特任教員 (30180962)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: Epstein-Barr virus (EBV) / 再活性化 / 抗体産生 / バセドウ病 / 自己免疫疾患 / IgM / IgG4 / 活性化誘導シチジンデアミナーゼ (AID)

Outline of Final Research Achievements

Epstein-Barr virus (EBV) is a ubiquitous herpes virus mainly persists in human B cells, and most adults have its antibodies. In the present study, we confirmed that EBV-infected B cells differentiated to plasma cells to produce antibodies along with EBV reactivation. In the EBV reactivation-induced Ig production, an activation-induced cytidine deaminase (AID) is induced, and thus class-switched antibodies including IgG, IgE, and IgG4 are produced as well as IgM which is the original isotype expressed on B cell surface.
TRAb, the causative autoantibodies of Graves’ disease, are produced in EBV reactivation-induced Ig production. Our results showed that TRAb produced without germinal center or bone marrow may play important roles in development and exacerbation of Graves’ disease. We constructed a new ELISA test to know clinical condition of Graves’ disease and obtained a patent (No. 6667806).

Free Research Field

ウイルス学と免疫学の視点から、自己免疫やアレルギーを研究しています。

Academic Significance and Societal Importance of the Research Achievements

今回の研究によって、遺伝因子の関与が大きいといわれてきたバセドウ病の原因として環境因子のひとつであるEBV感染と、その再活性化が重要であることが示された。
EBV再活性化に誘導される抗体産生系は、従来の骨髄・胚中心を介する抗体産生系とは別の抗体産生系である。EBV再活性化に誘導される抗体産生系は、特に自己抗体を産生しやすい傾向があり、今後種々の自己免疫疾患の発症機序の解明においても、さらに研究されるべき分野である、ということが示された。