Different contribution of class IIHLA in fulminant and typical autoimmune type 1 diabetes mellitus
Different contribution of class IIHLA in fulminant and typical autoimmune type 1 diabetes mellitus
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DOI：
10.1007/s00125-004-1626-x
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发表时间：
2005-02-01
期刊：
影响因子：
8.2
通讯作者：
Makino, H
中科院分区：
文献类型：
--
作者：
Imagawa, A;Hanafusa, T;Makino, H
目的/假设：暴发性1型糖尿病的特征是糖尿病的明显急性发作和缺乏胰岛相关自身抗体，占日本1型糖尿病的20%。我们的目的是澄清HLA亚型的贡献，暴发型1型糖尿病在日本。研究方法：对115例暴发型1型糖尿病、98例典型1A型糖尿病和190例正常对照者进行了HLA-A、- DR和- DQ血清学亚型检测。结果如下：暴发型1型糖尿病患者HLA-DR 4基因频率显著高于对照组，而DR 9基因频率无显著差异，HLA-DR 1、DR 2、DR 5和DR 8基因频率显著低于对照组。相比之下，在典型的1A型糖尿病中，DR 9而不是DR 4更常见，DR 2非常罕见。单倍型分析显示，在暴发型糖尿病中，DR 4-DQ 4的频率显著更高，DR 2-DQ 1和DR 8-DQ 1的频率较低。在1A型糖尿病中，DR 2-DQ 1非常罕见，而DR 9-DQ 3则明显更常见。在组合分析中，暴发性1型糖尿病中DR 4-DQ 4纯合子和典型1A型糖尿病中DR 9-DQ 3纯合子显示高优势比（分别为13.3和13.3）。结论/解释：我们的研究结果表明，II类HLA有助于暴发性1型糖尿病的发展。HLA亚型对1型糖尿病的易感性和抵抗性在暴发性和典型自身免疫性1型糖尿病之间是不同的。
Aims/hypothesis: Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. Methods: We determined the serological subtypes of HLA- A, - DR and - DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. Results: The frequency of HLA- DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA- DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4- DQ4 was significantly more frequent, and both DR2- DQ1 and DR8- DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2- DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4- DQ4 in fulminant type 1 diabetes and DR9- DQ3 in typical type 1A diabetes indicated high odds ratios ( 13.3 and 13.3, respectively). Conclusions/ interpretation: Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes.