Hampe C S, Hall T R, Agren A, Rolandsson O
Department of Medicine, University of Washington, Seattle, WA, USA.
Clin Exp Immunol. 2007 Apr;148(1):72-8. doi: 10.1111/j.1365-2249.2007.03334.x.
We analysed the beta cell-specific autoimmunity reflected in autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab) in the prediabetic period of GAD65Ab-positive healthy adults who developed Type 2 diabetes (T2D) during a follow-up period of 10 years. We found that of the adults that tested GAD65Ab-positive at baseline (n=25), six developed T2D and one developed Type 1 diabetes (T1D). Of the subjects that tested GAD65Ab-negative at baseline (n=2209), 81 developed T2D, one developed T1D and four developed unclassified diabetes, indicating that the risk for GAD65Ab-positive healthy adults to develop diabetes is increased sixfold. The GAD65Ab epitopes were characterized in a competition radioligand binding assay using recombinant Fab derived of GAD65-specific monoclonal antibodies. We observed that the GAD65Ab epitope specificities in the prediabetic period changed dynamically. Specifically, the binding to a middle and a C-terminal epitope increased during the follow-up period (P=0 x 03), causing a significant increase in the number of epitopes recognized (P=0 x 03). These findings are similar to previous observations of dynamic changes in the prediabetic period of schoolchildren at high risk for T1D development. However, the character of the epitopes differs between the two populations, suggesting differences in the beta cell-specific autoimmune response in the prediabetic period of patients with latent autoimmune diabetes in adults (LADA) and T1D.
我们分析了谷氨酸脱羧酶较小异构体自身抗体（GAD65Ab）所反映的β细胞特异性自身免疫，这些自身抗体来自在10年随访期内发展为2型糖尿病（T2D）的GAD65Ab阳性健康成年人的糖尿病前期。我们发现，在基线时检测GAD65Ab呈阳性的成年人中（n = 25），有6人发展为T2D，1人发展为1型糖尿病（T1D）。在基线时检测GAD65Ab呈阴性的受试者中（n = 2209），81人发展为T2D，1人发展为T1D，4人发展为未分类糖尿病，这表明GAD65Ab阳性健康成年人患糖尿病的风险增加了六倍。使用源自GAD65特异性单克隆抗体的重组Fab，通过竞争放射性配体结合试验对GAD65Ab表位进行了表征。我们观察到，糖尿病前期的GAD65Ab表位特异性会动态变化。具体而言，在随访期间，与中间和C端表位的结合增加（P = 0.03），导致识别的表位数量显著增加（P = 0.03）。这些发现与先前对有发展为T1D高风险的学童糖尿病前期动态变化的观察结果相似。然而，这两个人群的表位特征有所不同，这表明成人隐匿性自身免疫性糖尿病（LADA）和T1D患者糖尿病前期β细胞特异性自身免疫反应存在差异。
