Contribution of Antibodies Against IA-2β and Zinc Transporter 8 to Classification of Diabetes Diagnosed Under 40 Years of Age

Abstract

OBJECTIVE We investigated whether measuring autoantibodies against zinc transporter 8 (ZnT8A) and IA-2β (IA-2βA) may improve classification of new-onset type 1 diabetic patients based on detection of autoantibodies against insulin (IAA), GAD (GADA), and IA-2 (IA-2A). In addition, we studied the correlation of IA-2βA and ZnT8A with other biological and demographic variables. RESEARCH DESIGN AND METHODS Circulating autoantibodies were determined by liquid-phase radiobinding assays from 761 healthy control subjects and 655 new-onset (<1 week insulin) diabetic patients (aged 0–39 years) with clinical type 1 diabetes phenotype consecutively recruited by the Belgian Diabetes Registry. RESULTS At diagnosis, IA-2βA and ZnT8A prevalences were 41 and 58%, respectively. In IAA-negative, GADA-negative, and IA-2A–negative patients, one IA-2βA–positive and eleven ZnT8A-positive individuals were identified at the expense of eight and seven additional positive control subjects (1%), respectively, for each test. ZnT8A or IA-2βA screening increased (P < 0.001; McNemar) the number of patients with ≥2 antibodies both under (from 78 to 87% for ZnT8A and 82% for IA-2βA) and above age 15 (from 51 to 63% for ZnT8A and 56% for IA-2βA) versus 0% in control subjects. IA-2βA and ZnT8A were preferentially associated with IA-2A, and with younger age at diagnosis. Unlike ZnT8A, IA-2βA levels were positively correlated with HLA-DQ8 and negatively with HLA-DQ2. ZnT8A could replace IAA for classification of patients above age 10 without loss of sensitivity or specificity. CONCLUSIONS ZnT8A, and to a lesser degree IA-2βA, may usefully complement GADA, IA-2A, and IAA for classifying insulin-treated diabetes under age 40 years.