Comprehensive understanding for the relationship between HLA class II genes and chronic hepatitis B infection
| Project/Area Number |
16K09387
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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 |
Gastroenterology
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Nishida Nao 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (50456109)
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| Research Collaborator |
Sugiyama Masaya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | B型肝炎 / HLA / GWAS / HBワクチン / HBV / ゲノム / 感染症 / 遺伝学 / がん / B型肝炎ウイルス |
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| Outline of Final Research Achievements |
By conducting GWAS, the following were identified: host factors concerning responsiveness of hepatitis B vaccine (HB vaccine) and HBV related liver cancer. Specific HLA class II genotypes were associated with the responsiveness to Bimmugen, which is one of the widely used hepatitis B vaccine (HB vaccine) in Japan. Moreover, we revealed that BTNL2 gene contributed to the high response to the vaccine. Genome analysis (i.e. pathway analysis, upstream regulator analysis) based on detailed clinical information on vaccine responsiveness showed that recognition of HBV-derived peptide antigens by HLA molecules and transmission of costimulatory signals from antigen-presenting cells via costimulatory molecules such as BTNL2 molecules on T cells play important roles in HB vaccine responsiveness.
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| Academic Significance and Societal Importance of the Research Achievements |
ビームゲン接種者のうち約10%はその中和抗体であるHBs抗体を十分に獲得できないという問題がある。B型肝炎は血液汚染により引き起こされる疾患であるため、特に肝移植患者や医療従事者におけるHBs抗体陰性は早急な解決が求められる非常に重大な問題である。本研究で明らかとなったHBワクチン応答性に特異的に関連するHLA class II分子やワクチン高反応に関わるBTNL2分子を介したHBs抗体産生の機序を明らかにすることで、HBワクチンの適正かつ効率的な使用方法の確立が期待できる。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma2018
Author(s)
awai H, Nishida N, Sugiyama M, Murata K, Hino K, Nishina S, Matsumoto A, Tanaka E, Sakamoto N, Ogawa K, Yamamoto K, Tamori A, Yokosuka O, Kanda T, Sakaida I, Itoh Y, Eguchi Y, Oeda S, Mochida S, Yuen MF, Seto WK, Poovorawan Y, Posuwan N, Mizokami M, Tokunaga K
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Journal Title
Ｓｃｉ Ｒｅｐ
Volume: 8
Issue: 1
Pages: 7958-7958
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.2018
Author(s)
Nishida N, Sugiyama M, Sawai H, Nishina S, Sakai A, Ohashi J, Khor SS, Kakisaka K, Tsuchiura T, Hino K, Sumazaki R, Takikawa Y, Murata K, Kanda T, Yokosuka O, Tokunaga K, Mizokami M
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Journal Title
Hepatology
Volume: 印刷中
Issue: 3
Pages: 848-858
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] HLA-DRB1-DQB1 haplotypes and BTNL2 gene associate with response to a hepatitis B vaccine2017
Author(s)
Nao Nishida, Masaya Sugiyama, Hiromi Sawai, Sohji Nishina, Aiko Sakai, Keisuke Kakisaka, Keisuke Hino, Ryo Sumazaki, Yasuhiro Takikawa, Kazumoto Murata, Tatsuo Kanda, Osamu Yokosuka, Katsushi Tokunaga, and Masashi Mizokami
Organizer
American Association for the study of Liver Diseases The Liver Meeting 2017
Related Report
Int'l Joint Research
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