Analysis of disease-associated amino acid epitopes on HLA class II molecules in atopic dermatitis

• Published in: Journal of allergy and clinical immunology 1995, Vol.96 (6), p.1061-1068
• Main Authors: Saeki, Hidehisa, Kuwata, Shoji, Nakagawa, Hidemi, Etoh, Takafumi, Yanagisawa, Masami, Miyamoto, Mitsuko, Tokunaga, Katsushi, Juji, Takeo, Shibata, Yoichi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Allergic diseases; amino acid; Amino Acid Sequence; Amino Acids - immunology; atopic dermatitis; Base Sequence; Biological and medical sciences; Child; Dermatitis, Atopic - blood; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; epitope; Epitopes - analysis; Female; Genotype; HLA; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DQ beta-Chains; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; HLA-DRB1 Chains; Humans; IgE; Immunoglobulin E - blood; Immunopathology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Skin allergic diseases. Stinging insect allergies
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(95)70191-5

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-DRβ1 and DQβ1 domains revealed that DRβ1 71 Glu (RR = 5.71, p < 0.05) and DQβ1 30His (RR = 3.25 p < 0.01), and 57Val (RR = 3.13, p < 0.05) were increased in frequency. DRβ1 71Glu was exclusively unique to DRB1*1302. DQβ1 30His was shared by the following alleles: DQβ1*0501, *0502, *0503, and *0604, which were all increased in patients with AD. DQβ1 57 Val was shared by DQB1*0501 and *0604. A well-known haplotype, HLA-DRB1*1302-DQB1*0604, contains DRβ1 71Glu and DQβ1 30His and 57Val. Therefore HLA-DRβ1 71Glu and/or DQβ1 30His/ 57Val are considered to play the most important role in the development of atopic dermatitis. (J A LLERGY C LIN I MMUNOL 1995;96:1061-8.)