Sanjeevi C B, Hagopian W A, Landin-Olsson M, Kockum I, Woo W, Palmer J P, Lernmark A, Dahlquist G
Dept. of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Tissue Antigens. 1998 Mar;51(3):281-6. doi: 10.1111/j.1399-0039.1998.tb03103.x.
HLA DQA10301-DQB10302 (DQ8) and DQA10501-DQB10201 (DQ2) are positively and DQA10102-DQB10602 (DQ6) negatively associated with IDDM. In DQA10301-DQB10302 (DQ8)-positive patients, susceptibility is also mediated by DRB10401. 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 DRB10401 and not with DQA10301-DQB10302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA10301-DQB10302 (DQ8) and DRB10401. GAD65 autoantibodies, known to be closely associated with DQA10501-DQB10201 (DQ2)-DRB10301 haplotype, also showed no preferential association with DQA10301-DQB10302 (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.
HLA DQA10301 - DQB10302（DQ8）和DQA10501 - DQB10201（DQ2）与胰岛素依赖型糖尿病（IDDM）呈正相关，而DQA10102 - DQB10602（DQ6）与IDDM呈负相关。在携带DQA10301 - DQB10302（DQ8）的患者中，易感性也由DRB10401介导。本研究的目的是确定在425名0至15岁的瑞典IDDM儿童和367名对照中，HLA - DR4和DQ与谷氨酸脱羧酶65（GAD65）、胰岛细胞抗原512（ICA512）、胰岛素自身抗体以及胰岛细胞抗体（ICA）的存在之间的关联。我们发现，ICA512自身抗体主要与DRB10401相关，而与DQA10301 - DQB10302（DQ8）无关。胰岛素自身抗体则不存在这种层级关系，它与DQA10301 - DQB10302（DQ8）和DRB10401均相关。已知与DQA10501 - DQB10201（DQ2） - DRB10301单倍型密切相关的GAD65自身抗体，与DQA10301 - DQB10302（DQ8）相比，与DRB1*04也没有优先关联。这些结果表明，针对不同β细胞自身抗原的免疫反应可能通过来自不同基因座的HLA II类分子介导。抗原特异性免疫干预试验的设计应考虑这些HLA - DR和DQ亚型的关联。
