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.
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, University Hospital, Ghent, Belgium.
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Desombere
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Willems
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Leroux-Roels
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