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HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody positive first-degree relatives of type 1 diabetic patients.

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We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab+ siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab+. HLA-A*24 (P = 0.009), HLA-DQ2/DQ8 (P = 0.001), and positivity for IA-2A ± ZnT8A (P <0.001) were associated with development of T1D in multivariate analysis. The 5-year risk increased with the number of the above three markers present (n = 0: 6%; n = 1: 18%; n = 2: 46%; n = 3: 100%). Positivity for one or more markers identified a subgroup of 171 (59%) containing 88% of rapid progressors. The combined presence of HLA-A*24 and IA-2A+ ± ZnT8A+ defined a subgroup of 18 (6%) with an 82% diabetes risk. Among IA-2A+ ± ZnT8A+ relatives, identification of HLA-A*24 carriers in addition to HLA-DQ2/DQ8 carriers increased screening sensitivity for relatives at high Ab- and HLA-inferred risk (64% progression; P = 0.002). In conclusion, HLA-A*24 independently predicts rapid progression to T1D in Ab+ relatives and complements IA-2A, ZnT8A, and HLA-DQ2/DQ8 for identifying participants in immunointervention trials.
Tijdschrift: Diabetes
ISSN: 0012-1797
Volume: 62
Pagina's: 1345-1350
Jaar van publicatie:2013
Trefwoorden:HLA-A*24
  • ORCID: /0000-0003-4445-308X/work/156351544
  • ORCID: /0000-0002-8671-4527/work/117748368
  • ORCID: /0000-0001-7179-1717/work/83057849
  • ORCID: /0000-0003-4133-2565/work/76767020
  • ORCID: /0000-0003-2304-5298/work/61726068
  • ORCID: /0000-0002-6440-2485/work/61423566
  • ORCID: /0000-0002-9007-6177/work/60767618
  • ORCID: /0000-0002-9007-5203/work/58117059
  • Scopus Id: 84875411051
  • Institutional Repository URL: http://diabetes.diabetesjournals.org/content/62/4/1345.long
Toegankelijkheid:Open