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 the TCR A/D locus at human chromosome 14q11.2 have been implicated in susceptibility to specific allergies and the modulation of total serum IgE. It has also been hypothesized that HLA and TCR allelic interactions may have a strong 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 development of specific allergies.


METHODS
We performed an association study between HLA-DRB, HLA-DQB1 polymorphisms, D14S50 alleles, total serum IgE expression and specific allergies to house dust mite, grass pollens and cat fur. A sample of 181 individuals was drawn from a larger set of 2415 adults, sampled at random from a district in Nottingham.


RESULTS
Strong association was observed between HLA-DRB1*0701 allele and high total serum IgE expression (P < 0.001). D14S50 alleles alone showed no evidence for independent association. However, there was a significant interaction between DRB1*0701 and D14S50 allele 170 such that, when both were present, there was a further increase in total serum IgE levels.


CONCLUSIONS
This study suggests that DRB1*0701 allele is involved in the modulation of total serum IgE, and that there is an interaction between DRB1*0701 and a marker adjacent to TCR A/D in the control of IgE expression.
Mansur
A H
AH
Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St. James's University Hospital, Leeds, UK.
Williams
G A
GA
Bishop
D T
DT
Markham
A F
AF
Lewis
S
S
Britton
J
J
Morrison
J F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005819:Genetic Markers; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E