Zinc transporter 8 autoantibodies in fulminant, acute-onset, and slow-onset patients with type 1 diabetes

Zinc transporter 8 autoantibodies in fulminant, acute-onset, and slow-onset patients with type 1 diabetes
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DOI:
10.1002/dmrr.1269
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发表时间:
2011-11-01
影响因子:
8
通讯作者:
Eguchi, Katsumi
Eguchi, Katsumi
中科院分区:
医学2区
文献类型:
--
作者:
Kawasaki, Eiji;Nakamura, Kan;Eguchi, Katsumi

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背景本研究的目的是确定锌转运蛋白8(ZnT 8A)自身抗体在日本1型糖尿病患者的三种形式(暴发型,急性发作型和缓慢发作型)的患病率和作用。方法对196例新发1型糖尿病患者进行了研究:85例暴发型,81例急性发作型和30例缓慢发作型1型糖尿病。ZnT 8A通过使用携带325 Trp和325 Arg的杂合ZnT 8羧基末端构建体(aa 268 -369)的放射免疫测定来测定。此外,ZnT 8A表位分析使用ZnT 8构建纳入已知的aa 325变体(Trp,Arg和Gln)。结果ZnT 8A在58%的急性发作的1型糖尿病患者和20%的慢性发作的1型糖尿病患者中被检测到(p < 0.0005)。相比之下,没有来自暴发性1型糖尿病的血清对ZnT 8构建体具有反应性。Arg或Trp在aa 325位转化为Gln后,59%的发病年龄> 10岁的患者的反应性消失,显著高于10岁以上的患者。
Background The aim of this study was to determine the prevalence and role of autoantibodies to zinc transporter 8 (ZnT8A) in three forms (fulminant, acute-onset, and slow-onset) of Japanese patients with type 1 diabetes.Methods One-hundred and ninety-six new-onset patients with type 1 diabetes were studied: 85 were fulminant, 81 acute-onset, and 30 slow-onset type 1 diabetes. ZnT8A were determined by radioimmunoassay using a hybrid ZnT8 carboxy-terminal construct (aa268-369) carrying 325Trp and 325Arg. Furthermore, ZnT8A epitopes were analysed using ZnT8 constructs incorporating the known aa325 variants (Trp, Arg, and Gln).Results ZnT8A were detected in 58% patients with acute-onset and 20% with slow-onset type 1 diabetes (p < 0.0005). In contrast, none of sera from fulminant type 1 diabetes were reactive to ZnT8 construct. Conversion of Arg or Trp to Gln at aa325 abolished reactivity in 59% of patients with an age of onset > 10 years, which was significantly higher than that in patients