Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki, Japan.
Clin Immunol. 2011 Feb;138(2):146-53. doi: 10.1016/j.clim.2010.10.007. Epub 2010 Nov 10.
The aim of this study was to evaluate the humoral autoreactivity to zinc transporter 8 (ZnT8) depending on the clinical phenotype of type 1 diabetes (T1D). ZnT8 autoantibodies (ZnT8A) were determined by radioimmunoassay using carboxy-terminal ZnT8 constructs in 57 childhood-onset, 97 adult-onset, and 85 fulminant T1D. The ZnT8A frequency was higher in childhood-onset patients and decreased with increasing age of onset from 70% to 24% (P(trend)<0.005). None of the patients with fulminant T1D was positive for ZnT8A. There were at least two distinct ZnT8A epitope patterns associated with the aa325-restriction, childhood-onset patients have aa325-nonrestricted response more frequently compared to the adult-onset group (P<0.05). The level of ZnT8A was inversely associated with the copy number of HLA-DR4 allele (P<0.05). These results suggest differences in the humoral autoreactivity to ZnT8 depending on the clinical phenotype, which should provide strategy for autoantibody measurement in subjects to allow early diagnosis of autoimmune T1D.
本研究旨在评估锌转运体 8（ZnT8）的体液自身反应性与 1 型糖尿病（T1D）的临床表型的关系。采用放射性免疫分析法，使用羧基末端 ZnT8 构建物，在 57 例儿童起病、97 例成人起病和 85 例暴发性 T1D 患者中测定 ZnT8 自身抗体（ZnT8A）。在儿童起病患者中，ZnT8A 频率更高，并随着发病年龄的增加从 70%降至 24%（P（趋势）<0.005）。无一例暴发性 T1D 患者 ZnT8A 阳性。存在至少两种与 aa325 限制相关的不同 ZnT8A 表位模式，与成人起病组相比，儿童起病患者更频繁地出现 aa325 非限制反应（P<0.05）。ZnT8A 水平与 HLA-DR4 等位基因拷贝数呈负相关（P<0.05）。这些结果表明，ZnT8 的体液自身反应性因临床表型而异，这应为自身抗体测量策略提供依据，以允许对自身免疫性 T1D 患者进行早期诊断。
