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

• Published in: Diabetes/metabolism research and reviews 2011-11, Vol.27 (8), p.895-898
• Main Authors: Kawasaki, Eiji, Nakamura, Kan, Kuriya, Genpei, Satoh, Tsuyoshi, Kobayashi, Masakazu, Kuwahara, Hironaga, Abiru, Norio, Yamasaki, Hironori, Matsuura, Nobuo, Miura, Junnosuke, Uchigata, Yasuko, Eguchi, Katsumi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Age of Onset; Amino Acid Substitution; Asian Continental Ancestry Group; Autoantibodies; Autoantibodies - blood; Biomarkers - blood; Cation Transport Proteins - genetics; Cation Transport Proteins - immunology; Child; Diabetes mellitus; Diabetes Mellitus, Type 1 - immunology; Epitopes; Epitopes - immunology; Female; fulminant; Humans; Hybrids; Japanese; Male; Middle Aged; Radioimmunoassay; Reviews; slow-onset; type 1 diabetes; zinc transporter; Zinc Transporter 8; ZnT8
• ISSN: 1520-7552; 1520-7560; 1520-7560
• DOI: 10.1002/dmrr.1269

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. Copyright © 2011 John Wiley & Sons, Ltd.