Evidence for a role of HLA DRB1 alleles in the control of IgE levels, strengthened by interacting TCR A/D marker alleles

Background MHC class II alleles at human chromosome 6p21.1 and alleles in t he TCR A/D locus at human chromosome 14q11.2 have been implicated in suscep tibility to specific allergies and the modulation of total serum IgE. It ha s also been hypothesized that HLA and TCR allelic interactions may have a s trong influence on predisposition to allergic disease. Objective This study was performed to investigate the influence of HLA-DRB and DQB1 alleles and D14S50 alleles (adjacent to TCR A/D locus on 14q11.2), individually and in-combination, on total serum IgE levels, and on the dev elopment of specific allergies. Methods We performed an association study between HLA-DRB, HLA-DQB1 polymor phisms, D14S50 alleles, total serum IgE expression and specific allergies t o house dust mite, grass pollens and cat fur. A sample of 181 individuals w as drawn from a larger set of 2415 adults, sampled at random from a distric t in Nottingham. Results Strong association was observed between HLA-DRB1*0701 allele and hi gh total serum IgE expression (P < 0.001). D14S50 alleles alone showed no e vidence for independent association. However, there was a significant inter action between DRB1*0701 and D14S50 allele 170 such that, when both were pr esent, there was a further increase in total serum IgE levels. Conclusion This study suggests that DRB1*0701 allele is involved in the mod ulation of total serum IgE, and that there is an interaction between DRB1*0 701 and a marker adjacent to TCR A/D in the control of IgE expression.