title: SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes.
abstract: Type 1A diabetes (T1D) results from autoimmunity targeted at a limited number of molecules that are expressed in the pancreatic beta 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.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado 80045, USA. janet.wenzlau@uchsc.edu
authors.forename: Janet M
authors.initials: JM
authors.lastname: Wenzlau
authors.forename: Ong
authors.initials: O
authors.lastname: Moua
authors.forename: Suparna A
authors.initials: SA
authors.lastname: Sarkar
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Howard W
authors.initials: HW
authors.lastname: Davidson
authors.forename: John C
authors.initials: JC
authors.lastname: Hutton
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D027682:Cation Transport Proteins / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D011379:Prognosis; D012680:Sensitivity and Specificity; D016036:Seroepidemiologic Studies; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8