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SlC30A8 Is a Major Target of Humoral Autoimmunity in Type 1 Diabetes and a Predictive Marker in Prediabetes


Address for correspondence: Janet M. Wenzlau, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Mailstop B140, PO Box 6511, Aurora, CO 80045. Voice: +303-724-6815; fax: +303-724-6816.


Type 1A diabetes (T1D) results from autoimmunity targeted at a limited number of molecules that are expressed in the pancreatic β cell. Putative novel autoantigen candidates were identified from microarray expression profiling of human and rodent islet cells. The highest ranking candidate was Slc30A8 (zinc transporter 8; ZnT8), which was screened by radioimmunoprecipitation assays against new-onset T1D and prediabetic sera. Such assays detected 63% of subjects with new-onset diabetes, but fewer than 2% of controls, 3% of those with type 2 diabetes, and 10% of patients with other autoimmune disorders. ZnT8 autoantibodies were found, however, in 26% of T1D subjects previously classified as autoantibody-negative on the basis of existing markers (GADA, IA2 A, IAA, and ICA). We conclude that SLC30A8 provides an important additional and independent predictive marker for T1D.