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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.

Authors
  • Mbunwe, Eric
  • Van der Auwera, Bart J
  • Vermeulen, Ilse
  • Demeester, Simke
  • Van Dalem, Annelien
  • Balti, Eric V
  • Van Aken, Sara
  • Derdelinckx, Luc
  • Dorchy, Harry
  • De Schepper, Jean
  • van Schravendijk, Chris
  • Wenzlau, Janet M
  • Hutton, John C
  • Pipeleers, Daniël
  • Weets, Ilse
  • Gorus, Frans K
Type
Published Article
Journal
Diabetes
Publisher
American Diabetes Association
Publication Date
Apr 01, 2013
Volume
62
Issue
4
Pages
1345–1350
Identifiers
DOI: 10.2337/db12-0747
PMID: 23160529
Source
Medline
License
Unknown

Abstract

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.

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