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.
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.
Sanjeevi
C B
CB
Dept. of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. sanjeevi.carani@molmed.ki.se
Hagopian
W A
WA
Landin-Olsson
M
M
Kockum
I
I
Woo
W
W
Palmer
J P
JP
Lernmark
A
A
Dahlquist
G
G
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
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