Achenbach Peter, Warncke Katharina, Reiter Jürgen, Naserke Heike E, Williams Alistair J K, Bingley Polly J, Bonifacio Ezio, Ziegler Anette-G
Diabetes Research Institute and 3rd Medical Department, Hospital München-Schwabing, Munich, Germany.
Diabetes. 2004 Feb;53(2):384-92. doi: 10.2337/diabetes.53.2.384.
Family history of type 1 diabetes and autoantibodies to the islet antigens insulin (IAA), glutamate decarboxylase (GADA), and the protein tyrosine phosphatase-like protein IA-2 (IA-2A) are strong predictors of type 1 diabetes, but the rate of progression to diabetes in multiple islet autoantibody-positive relatives varies widely. We asked whether detailed characterization of islet autoantibodies that included determination of titer, epitope specificity, and IgG subclass would improve diabetes prediction in a large cohort of autoantibody-positive relatives. The study shows a strong association between risk and high titer, broad antibody responses to IA-2 and insulin. The highest risks were associated with high-titer IA-2A and IAA, IgG2, IgG3, and/or IgG4 subclass of IA-2A and IAA, and antibodies to the IA-2-related molecule IA-2beta. Using models based on these antibody characteristics, autoantibody-positive relatives can be classified into groups with risks of diabetes ranging from 7 to 89% within 5 years.
1型糖尿病家族史以及针对胰岛抗原胰岛素（IAA）、谷氨酸脱羧酶（GADA）和蛋白酪氨酸磷酸酶样蛋白IA-2（IA-2A）的自身抗体是1型糖尿病的有力预测指标，但多个胰岛自身抗体阳性亲属发展为糖尿病的速率差异很大。我们询问，对胰岛自身抗体进行详细表征，包括测定滴度、表位特异性和IgG亚类，是否会改善一大群自身抗体阳性亲属的糖尿病预测。该研究显示风险与高滴度、对IA-2和胰岛素的广泛抗体反应之间存在密切关联。最高风险与高滴度IA-2A和IAA、IA-2A和IAA的IgG2、IgG3和/或IgG4亚类以及针对IA-2相关分子IA-2β的抗体有关。使用基于这些抗体特征的模型，自身抗体阳性亲属可被分为5年内糖尿病风险从7%到89%不等的组。
