title: Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8.
abstract: HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. In DQA1*0301-DQB1*0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1*0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0-15 years. We found that ICA512 autoantibodies were associated primarily with DRB1*0401 and not with DQA1*0301-DQB1*0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1*0301-DQB1*0302 (DQ8) and DRB1*0401. GAD65 autoantibodies, known to be closely associated with DQA1*0501-DQB1*0201 (DQ2)-DRB1*0301 haplotype, also showed no preferential association with DQA1*0301-DQB1*0302 (DQ8) versus DRB1*04. These results suggest that the immune response to different beta-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.
authors.affiliation: Dept. of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. sanjeevi.carani@molmed.ki.se
authors.forename: C B
authors.initials: CB
authors.lastname: Sanjeevi
authors.forename: W A
authors.initials: WA
authors.lastname: Hagopian
authors.forename: M
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: W
authors.initials: W
authors.lastname: Woo
authors.forename: J P
authors.initials: JP
authors.lastname: Palmer
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: G
authors.initials: G
authors.lastname: Dahlquist
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology*; D006801:Humans; D007223:Infant; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D013548:Sweden
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D015804:HLA-DR4 Antigen; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases