title: 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.
  
  
  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.
authors.affiliation: Brussels Free University, Brussels, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Vermeulen
authors.forename: Ilse
authors.initials: I
authors.lastname: Weets
authors.forename: Milca
authors.initials: M
authors.lastname: Asanghanwa
authors.forename: Johannes
authors.initials: J
authors.lastname: Ruige
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.forename: Vito
authors.initials: V
authors.lastname: Lampasona
authors.forename: Janet M
authors.initials: JM
authors.lastname: Wenzlau
authors.forename: John C
authors.initials: JC
authors.lastname: Hutton
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: Frans K
authors.initials: FK
authors.lastname: Gorus
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D027682:Cation Transport Proteins / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000145:classification* / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology*; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C096322:ICA512 autoantibody; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8