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Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.

Abstract
In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A(+) and/or ZnT8A(+) relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.
AuthorsF K Gorus, E V Balti, I Vermeulen, S Demeester, A Van Dalem, O Costa, H Dorchy, S Tenoutasse, T Mouraux, C De Block, P Gillard, K Decochez, J M Wenzlau, J C Hutton, D G Pipeleers, I Weets, Belgian Diabetes Registry
JournalClinical and experimental immunology (Clin Exp Immunol) Vol. 171 Issue 1 Pg. 82-90 (Jan 2013) ISSN: 1365-2249 [Electronic] England
PMID23199327 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2012 British Society for Immunology.
Chemical References
  • Autoantibodies
  • Blood Glucose
  • Cation Transport Proteins
  • Insulin
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • PTPRN protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
Topics
  • Adolescent
  • Autoantibodies (blood, economics)
  • Belgium
  • Blood Glucose (immunology)
  • Cation Transport Proteins (immunology)
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 (blood, immunology)
  • Disease Progression
  • Family
  • Female
  • Glutamate Decarboxylase (immunology)
  • Humans
  • Insulin (immunology)
  • Male
  • Prediabetic State (blood, immunology)
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 (immunology)
  • Registries
  • Risk
  • Zinc Transporter 8

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