Comprehensive understanding for the relationship between HLA class II genes and chronic hepatitis B infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Center for Global Health and Medicine
• 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)
• Research Collaborator: Sugiyama Masaya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: B型肝炎 / HLA / GWAS / HBワクチン

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.

Free Research Field

ゲノム医科学

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。