Analysis of disease-associated amino acid epitopes on HLA class II molecules in atopic dermatitis.
We investigated the association between HLA class II alleles and severe atopic dermatitis with high serum IgE levels (greater than 8000 U/ml). The frequencies of HLA-DRB1*1302 and DQB1*0604 were increased, whereas the frequency of HLA-DQB1*0302 was decreased. A strong haplotype, HLA-DRB1*1302-DQB1*0604, has been reported in the Japanese population, and this haplotype is conserved in patients with AD. Further analysis of the amino acid epitopes on the HLA-DR beta 1 and DQ beta 1 domains revealed that DR beta 1 71Glu (RR = 5.71, p < 0.05) and DQ beta 1 30His (RR = 3.25 p < 0.01), and 57Val (RR = 3.13, p < 0.05) were increased in frequency. DR beta 1 71Glu was exclusively unique to DRB1*1302. DQ beta 1 30His was shared by the following alleles: DQ beta 1*0501, *0502, *0503, and *0604, which were all increased in patients with AD. DQ beta 1 57Val was shared by DQB1*0501 and *0604. A well-known haplotype, HLA-DRB1*1302-DQB1*0604, contains DR beta 1 71Glu and DQ beta 1 30His and 57Val. Therefore HLA-DR beta 1 71Glu and/or DQ beta 1 30His/57Val are considered to play the most important role in the development of atopic dermatitis.
Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
H
H
Saeki
S
S
Kuwata
H
H
Nakagawa
T
T
Etoh
M
M
Yanagisawa
M
M
Miyamoto
K
K
Tokunaga
T
T
Juji
Y
Y
Shibata
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology; D001483:Base Sequence; D002648:Child; D003876:Dermatitis, Atopic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D000596:Amino Acids; D000939:Epitopes; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007073:Immunoglobulin E