Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen

Abstract

Two HLA class II haplotypes, HLA-[DQB1*0602; DQA1*0102; DR15] and HLA-[DQB1*0603; DQA1*0103; DRB1*1301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB1*0604; DQA1*0102; DRB1*1302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB1*06 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB1*0602 and *0603 and the nonresponder allele *0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB1*1301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB1*06 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.

Pediatric and adult forms of type I autoimmune hepatitis in argentina: Evidence for differential genetic predisposition

“…22 Furthermore, in a recent report, Val 86 of the HLA-DR␤ chain was postulated to also determine the response against hepatitis B surface antigen. 23 In this study, HLA-DRB1*1301 and HLA-DR15 alleles were found as the responder alleles, but HLA-DRB1*1302 was associated with nonresponse to hepatitis B surface antigen. Additional evidence for the role of position 86 of the HLA-DR␤ chain in controlling immune responses came from studies performed in Gambia, West Africa.…”

T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

“…Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response non-responsiveness (HBsAg titer < 10 kU/L) to vaccination are associated with certain human leukocyte antigen (HLA)-class Ⅱ alleles. DRB1*0301, DRB1*0701, and DQB1*0201 [5,8,9] were shown to have a higher prevalence in non-responders, whereas other antigens (DRB1*0101, *1301, *1501, and DPB1*0401) seem to mediate strong immune responses [9][10][11][12] . Higher age, obesity, male gender, smoking, and chronic dialysis are risk factors for a non-/ low-responsiveness [8,9,[13][14][15] .…”

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

“…In many of the non-responders not explained by the above risk factors, certain HLA types have been found to be associated with non response [16][17][18][19] . The relationship of hepatitis B vaccination response with age is controversial.…”

“…A non-response was defined as mean antiHBs antibody titers below 10 IU/L, low responders were those with titers between 10-99 IU/L, and those with anti-HBs titers more than 100 IU/L [13][14][15][16][17][18][19][20][21][22][23][24][25][26] were responders. A high response was on with titers more than 1 000 IU/l.…”