Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth.
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.
Li
Yufeng
Y
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ni
Rong
R
Song
Wei
W
Shao
Wenshuo
W
Shrestha
Sadeep
S
Ahmad
Sushma
S
Cunningham
Coleen K
CK
Flynn
Patricia M
PM
Kapogiannis
Bill G
BG
Wilson
Craig M
CM
Tang
Jianming
J
D000293:Adolescent; D000704:Analysis of Variance; D000917:Antibody Formation / Q000235:genetics*; D044383:Black People / Q000235:genetics; D001938:Brazil; D005260:Female; D014644:Genetic Variation; D018023:HIV Seronegativity; D006681:HLA-D Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult; D001741:Black or African American
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D017325:Hepatitis B Vaccines