Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.

Approximately 5-10% of individuals, who are vaccinated with a hepatitis B (HB) vaccine designed based on the HBV genotype C, fail to acquire protective levels of antibodies. Here, host genetic factors behind low immune response to this HB vaccine were investigated by a genome wide association study (GWAS) and HLA association tests. A GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders, 351 intermediate responders, and 735 high responders. Classical HLA class II alleles were statistically imputed using the genome-wide SNP typing data. The GWAS identified independent associations of HLA-DRB1-DQB1, HLA-DPB1 and BTNL2 genes with immune response to a HB vaccine designed based on the HBV genotype C. Five HLA-DRB1-DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1-DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1-DQB1 haplotypes, and no association was identified for any of the DPB1 alleles. In contrast, no association was identified for DRB1-DQB1 haplotypes and DPB1 alleles in a comparison between high immune responders and healthy individuals. The findings in this study clearly show the importance of HLA-DR-DQ (i.e. recognition of a vaccine related HB surface antigen (HBsAg) by specific DR-DQ haplotypes) and BTNL2 molecules (i.e. high immune response to HB vaccine) for response to a HB vaccine designed based on the HBV genotype C. This article is protected by copyright. All rights reserved.