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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients
Diabetes, Volume 62, No. 4, Year 2013
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Description
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+ 6 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. © 2013 by the American Diabetes Association.
Authors & Co-Authors
Mbunwe, Eric
Belgium, Brussels
Vrije Universiteit Brussel
van der Auwera, Bart J.R.
Belgium, Brussels
Vrije Universiteit Brussel
Balti Vounsia, Eric
Belgium, Brussels
Vrije Universiteit Brussel
de Schepper, Jean A.
Belgium, Brussels
Free Universities of Brussels
van Schravendijk, Christiaan F.H.
Belgium, Brussels
Vrije Universiteit Brussel
Wenzlau, Janet M.
United States, Aurora
University of Colorado Anschutz Medical Campus
Hutton, John C.
United States, Aurora
University of Colorado Anschutz Medical Campus
Pipeleers, Daniël G.
Belgium, Brussels
Vrije Universiteit Brussel
Weets, Ilse
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Brussels
Free Universities of Brussels
Gorus, Frans K.
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Brussels
Free Universities of Brussels
Statistics
Citations: 22
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.2337/db12-0747
ISSN:
1939327X
Research Areas
Noncommunicable Diseases