Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India

INTRODUCTION: Zinc transporter-8 (ZnT8) is an islet cell secretory granule membrane protein recently identified as an autoantigen in type 1 diabetes (T1D). The aim of this study was to estimate the prevalence of antibodies to ZnT8 (ZnT8A) in juvenile onset T1D and to determine the utility of ZnT8A as an independent marker of autoimmunity either alone in antibody-negative subjects or in conjunction with glutamic acid decarboxylase (GAD) and insulinoma-2 antigen antibodies (GADA and IA2A). RESEARCH DESIGN: ZnT8A, GADA, and IA2A were measured in sera of consecutive T1D patients (n = 88, age range 2-18 years) within 4 years of diagnosis and 88 sex-matched controls. RESULTS: The prevalences of GADA, ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. IA2A were positive only in two patients who were negative for other two antibodies. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. In receiver operating characteristic (ROC) analysis, the performances of GADA and ZnT8As were better than that of IA2A; and AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59, respectively. CONCLUSIONS: ZnT8A complements GADA and increases the diagnostic sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of ZnT8A increases the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian T1D patients without loss of sensitivity and specificity.