Relationship of HLA-DQA1 alleles and humoral antibody following measles vaccination

Abstract

Background: The human leukocyte antigen (HLA)-DQA1 locus is only moderately polymorphic compared to other HLA class II loci; however, we hypothesized that these polymorphisms could be important in determining the humoral antibody response to measles vaccine virus.

Methods: The seroprevalence of measles antibody was determined in 881 school children who had been immunized with MMR-II at age approximately 15 months. All subjects resided in a geographic area with no circulating measles virus. The IgG antibody levels were determined by a measles-specific whole virus enzyme immunoassay (EIA) (BioWhittaker, Walkersville, MD). Subjects who were nonresponders (IgG seronegative or equivocal) (n = 46) and hyperresponders (upper 10th percentile of IgG levels of all subjects) (n = 64) were HLA-DQA1 typed using polymerase chain reaction with sequence-specific primers (PCR-SSP). The HLA-DQA1 allele frequencies, as well as homozygosity rates, were compared between the nonresponders and hyperresponders.

Results: The overall allele frequency distribution of alleles between the nonresponders and hyperresponders was significantly different (P = 0.05), with nonresponders having an excess of HLA-DQA1*05 alleles (P = 0.017) and hyperresponders having an excess of HLA-DQA1*01 alleles (P = 0. 016). The homozygosity rate among nonresponders was significantly higher than among hyperresponders (23.9% vs. 9.4%, P = 0.037).

Conclusion: HLA-DQA1 alleles have important associations with the antibody response to measles vaccine. Specifically, the carriage of the HLA-DQA1*05 alleles is associated with nonresponse and that of HLA-DQA1*01 alleles with hyperresponse. In addition, HLA-DQA1 homozygosity is significantly associated with poor antibody response to measles vaccine.