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 (CO), 97 adult-onset (AO), and 85 fulminant T1D. The ZnT8A frequency was higher in CO patients and decreased with increasing age of onset from 70% to 24% (P trend <0.005). None of patients with fulminant T1D were positive for ZnT8A. There were at least two distinct ZnT8A epitope patterns associated with the aa325-restriction, CO patients have aa325-nonrestricted response more frequently compared to the AO 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.
These results indicate that the determination of IAA, IA-2icA, and ZnT8A improves the prediction of a future insulin insufficiency in adult-onset autoimmune diabetes, which appears to be superior to GADA titer and GAD65A-specific epitopes.
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