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

Diabetes Metab Res Rev. 2011 Nov;27(8):895-8. doi: 10.1002/dmrr.1269.

Abstract

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≤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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • Asians
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / immunology*
  • Child
  • Diabetes Mellitus, Type 1 / immunology*
  • Epitopes / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Radioimmunoassay
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • Biomarkers
  • Cation Transport Proteins
  • Epitopes
  • SLC30A8 protein, human
  • Zinc Transporter 8