EBV reactivation-induced autoantibody production and management of Graves' disease
| Project/Area Number |
17K08694
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tottori University |
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Principal Investigator |
NAGATA Keiko 鳥取大学, 医学部, 講師 (50304209)
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| Co-Investigator(Kenkyū-buntansha) |
林 一彦 鳥取大学, 医学部, 特任教員 (30180962)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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) / Epstein-Barr ウイルス (EBV) / TSHレセプター抗体 (TRAb) / Epstein-Barrウイルス(EBV) / TSHレセプター抗体（TRAb） / 女性ホルモン / AID / TRAb / EBウイルス / TRAbアイソタイプ / 自己反応性B細胞 |
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| 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).
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| 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。
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Report
(5 results)
Research Products
(29 results)
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[Journal Article] Epstein-Barr Virus Lytic Reactivation Induces IgG4 Production by Host B Lymphocytes in Graves' Disease Patients and Controls: A Subset of Graves' Disease Is an IgG4-Related Disease-Like Condition.2018
Author(s)
Nagata K, Hara S, Nakayama Y, Higaki K, Sugihara H, Kuwamoto S, Matsushita M, Kato M, Tanio S, Ishiguro K, Hayashi K.
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Journal Title
Viral Immunoogy
Volume: 31 (8)
Issue: 8
Pages: 540-547
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease2017
Author(s)
Nagata, K. Kumata, K. Nakayama, Y. Satoh, Y. Sugihara, H. Hara, S. Matsushita, M. Kuwamoto, S. Kato, M. Murakami, I. Hayashi, K.
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Journal Title
Viral Immunol
Volume: 30
Issue: 3
Pages: 240-249
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Thyrotropin receptor antibodies (TRAbs) induced by Epstein-Barr virus reactivation: Significance on Graves’ disease2021
Author(s)
Keiko Nagata, Kazuhiko Hayashi, Yukio Satoh, Mitsuhiko Osaki, Junichiro Miake, Yoshinori Ichihara, Tatsuya Sawano, Yuhang Zhou, Agung Kurniawan Priyono, Kazuhiko Matsuzawa, Takeshi Imamura
Organizer
第94回 日本薬理学会年会
Related Report
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[Presentation] Association of Hedgehog signal expression with MCPyV infection and outcome in Merkel cell carcinoma.2017
Author(s)
Matsushita M, Kuromi T, Iwasaki T, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K.
Organizer
29th European Congress of Pathology, Amsterdam, Netherlands
Related Report
Int'l Joint Research
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