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首页> 外文期刊>EBioMedicine >Subtyping of Type 1 Diabetes as Classified by Anti-GAD Antibody, IgE Levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese
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Subtyping of Type 1 Diabetes as Classified by Anti-GAD Antibody, IgE Levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese

机译：在日本，按抗GAD抗体，IgE水平和酪氨酸激酶2（TYK2）启动子变异分类的1型糖尿病亚型

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Objective: Type 1 diabetes (T1D) is known to be caused by Th1 cell-dependent autoimmunity. Recently, we reported that TYK2 promoter variant serves as a putative virus-induced diabetes susceptibility gene associated with deteriorated interferon-dependent antiviral response. TYK2 is also related to HIES, that is, Th2 cell-dependent. Therefore, TYK2 promoter variant may be also associated with the pathogenesis of T1D, modulating Th1/Th2 balance. Research Design and Methods: We assessed the association between anti- GAD Ab, IgE levels, and TYK2 promoter variant among 313 T1D patients, 184 T2D patients, and 264 YH controls in the Japanese. Results: T1D patients had elevated IgE (median, 56.7U/ml; p<0.0001) compared with T2D patients (22.5U/ml) and controls (43.3U/ml). Contrary to our expectations, there was no correlation between TYK2 promoter variant and IgE levels. We found that T1D could be subtyped as four groups based on anti-GAD Ab and IgE profile: Subtype 1, anti-GAD Ab positive and non-elevated IgE (47.0%); Subtype 2, anti-GAD Ab negative and non-elevated IgE (35.1%); Subtype 3, anti-GAD Ab positive and elevated IgE (10.9%); and Subtype 4, anti-GAD Ab negative and elevated IgE (7.0%). In Subtype 2, a significantly higher incidence was observed in T1D cases carrying the TYK2 promoter variant (OR, 2.60; 95%CI, 1.03-6.97; p=0.032), and also showing a flu-like syndrome at diabetes onset (OR, 2.34; 95%CI, 1.27-4.35; p=0.003). Interpretation: Anti-GAD Ab and IgE profiling helps classifying T1D into four groups that recognize variable pathogenic bases of T1D.
机译：目的：已知1型糖尿病（T1D）由Th1细胞依赖性自身免疫引起。最近，我们报道了TYK2启动子变异体作为推定的病毒诱导的糖尿病易感基因，与干扰素依赖性抗病毒反应恶化相关。 TYK2也与HIES相关，即Th2细胞依赖性。因此，TYK2启动子变体也可能与T1D的发病机制有关，从而调节Th1 / Th2平衡。研究设计和方法：我们评估了313位T1D患者，184位T2D患者和264位YH对照人群中抗GAD Ab，IgE水平和TYK2启动子变异之间的关联。结果：与T2D患者（22.5U / ml）和对照组（43.3U / ml）相比，T1D患者的IgE升高（中位数为56.7U / ml; p <0.0001）。与我们的预期相反，TYK2启动子变体与IgE水平之间没有相关性。我们发现，根据抗GAD Ab和IgE概况，T1D可以分为四类：亚型1，抗GAD Ab阳性和未升高的IgE（47.0％）;亚型2，抗GAD Ab阴性和未升高的IgE（35.1％）;亚型3，抗GAD Ab阳性且IgE升高（10.9％）;亚型4，抗GAD Ab阴性，IgE升高（7.0％）。在亚型2中，在携带TYK2启动子变体的T1D病例中观察到明显更高的发病率（OR，2.60; 95％CI，1.03-6.97; p = 0.032），并且在糖尿病发作时也显示出流感样综合征（OR， 2.34; 95％CI，1.27-4.35; p ＝ 0.003）。解释：抗GAD Ab和IgE分析有助于将T1D分为识别T1D可变致病性碱基的四类。

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