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

Abstract

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 ≤10 years of age (33%, p < 0.05). Conclusions: These results suggest that ZnT8A are an additional useful marker for acute-onset type 1 diabetes, but not a diagnostic marker for fulminant type 1 diabetes, and ZnT8A epitope recognition is different according to the onset age. © 2011 John Wiley & Sons, Ltd.