Response to hepatitis B vaccine: multiple HLA genes are involved.
The mechanism underlying the impaired immune response to hepatitis B vaccines in up to 10% of healthy subjects is not known. An increased incidence of poor responsiveness in subjects with HLA-DR3+ or -DR7+ haplotypes has been documented, suggesting that HLA-DR-linked genes may regulate the human response to hepatitis B surface antigen. However, not all HLA-DR3+ and/or -DR7+ individuals are poor responders, and subjects with identical HLA-DR haplotypes sometimes display totally divergent antibody responses to vaccination. HLA class II DNA typing was performed in well and poorly responding hepatitis B vaccine recipients and we analyzed the role of the single HLA-DR, -DP, and -DQ molecules and of their associated (interaction) haplotypes in the response to hepatitis B vaccination. Statistical analysis revealed that HLA-DRB1*010*, -DR5, -DPB1*040*, -DQB1*0301, and -DQB1*0501 were more abundant in good responders, whereas HLA-DRB1*07, -DPB1*1101, and -DQB1*020* were associated with poor response, with DQB1*020* showing the strongest association with poor responsiveness. We further investigated whether there were interactions between the HLA factors contributing to poor responsiveness. We show here that HLA-DPB1*02 was negatively associated with responsiveness when it occurred in association with haplotype DRB1*0701/DRB4*0101-DQB1*020*, and DRB4*0101 was negatively associated with responsiveness when it occurred in association with haplotype DRB1*0301/DRB3*0101-DQB1*020*. Our results indicate that the immune response to hepatitis B vaccine is largely determined by HLA-DR, -DP, and -DQ genes and that interaction between HLA molecules that are not in linkage disequilibrium contributes to poor responsiveness.
Desombere
I
I
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, University Hospital, Ghent, Belgium.
Willems
A
A
Leroux-Roels
G
G
D000328:Adult; D006682:HLA-DP Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D010641:Phenotype
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D017325:Hepatitis B Vaccines