title: Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma).
abstract: HLA class II alleles (detected by DNA typing) were determined in 116 Caucasians with systemic sclerosis positive and negative for anticentromere autoantibodies (ACA). Significantly increased frequencies of HLA-DR5(DRw11) (P = 0.009) and the Dw13(DRB1*0403, *0407) subtypes of DR4 (probability corrected, Pc = 0.005) were seen in ACA positive patients, and HLA-DR1 and DRw8 were also increased. These findings appeared to reflect linkage disequilibrium of DR5(DRw11) and many DR4(Dw13) haplotypes with HLA-DQw7 and DR1 with DQw5. In fact, the presence of a DQB1 allele having a polar glycine or tyrosine at position 26 of the DQB1 first domain versus a hydrophobic leucine accounted for 100% of ACA positive Caucasian systemic sclerosis patients compared to 69% of the ACA negative SS patients (P = 0.0008) and 71% of Caucasian controls (P = 0.0003) as well as all 7 ACA patients of non-Caucasian background. Furthermore, the genotype frequency of DQB1 alleles lacking leucine at position 26 was 73% in ACA positive SS patients, compared to 42% of ACA negative patients (P = 1.2 x 10(-5)) and 38% of controls (P = 5.8 x 10(-7)). These data, then, suggest that the second hypervariable region of the HLA-DQB1 chain may form the candidate epitope associated with the ACA response.
authors.affiliation: Department of Internal Medicine, University of Texas Medical School, Houston 77225.
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
authors.forename: D
authors.initials: D
authors.lastname: Owerbach
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
authors.forename: R
authors.initials: R
authors.lastname: Moreda
authors.forename: R A
authors.initials: RA
authors.lastname: Isern
authors.forename: F C
authors.initials: FC
authors.lastname: Arnett
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000032:analysis*; D001483:Base Sequence; D002503:Centromere / Q000276:immunology*; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D012595:Scleroderma, Systemic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens