Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth

Hum Genet. 2009 Nov;126(5):685-96. doi: 10.1007/s00439-009-0720-z. Epub 2009 Jul 14.

Abstract

To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(-)) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration > or = 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV(+) youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines.

MeSH terms

  • Adolescent
  • African Continental Ancestry Group / genetics
  • Analysis of Variance
  • Antibody Formation / genetics*
  • Brazil
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Variation
  • HIV Seronegativity
  • HLA-D Antigens / genetics
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Haplotypes / genetics
  • Hepatitis B Vaccines / immunology
  • Hepatitis B Vaccines / therapeutic use*
  • Hispanic Americans / genetics
  • Humans
  • Male
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide
  • South Africa
  • United States
  • Young Adult

Substances

  • HLA-D Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Hepatitis B Vaccines