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

TitleClear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth.
Publication TypePublication
Year of Publication2009
AuthorsLi Y, Ni R, Song W, Shao W, Shrestha S, Ahmad S, Cunningham CK, Flynn PM, Kapogiannis BG, Wilson CM, Tang J
JournalHum Genet
Volume126
Issue5
Pagination685-96
Date Published2009 Nov
ISSN1432-1203
KeywordsAdolescent, African Continental Ancestry Group, Analysis of Variance, Antibody Formation, Brazil, European Continental Ancestry Group, Female, Genetic Variation, Haplotypes, Hepatitis B Vaccines, Hispanic Americans, HIV Seronegativity, HLA-D Antigens, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Male, Multivariate Analysis, Polymorphism, Single Nucleotide, South Africa, United States, Young Adult
Abstract

<p>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.</p>

DOI10.1007/s00439-009-0720-z
Alternate JournalHum. Genet.
PubMed ID19597844
PubMed Central IDPMC2771141
Grant ListK02 AI076123 / AI / NIAID NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
U01 HD040533 / HD / NICHD NIH HHS / United States