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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

HLA-A*24 Is an Independent Predictor of 5-Year Progression to Diabetes in Autoantibody-Positive First-Degree Relatives of Type 1 Diabetic Patients
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.
- Universitair Ziekenhuis Brussel Belgium
- Université Catholique de Louvain Belgium
- Université Libre de Bruxelles Belgium
- Vrije Universiteit Brussel Belgium
- Ghent University Hospital Belgium
HLA CLASS-I, Male, GENETIC SUSCEPTIBILITY, Adolescent, ZINC TRANSPORTER-8, AUTOIMMUNITY, HLA-A24 Antigen, Endocrinology & Metabolism, Young Adult, Métabolisme, Belgian Diabetes Registry, Risk Factors, Humans, Genetic Predisposition to Disease, COMBINATION, Child, 11 Medical and Health Sciences, Original Research, Autoantibodies, RISK, Diabétologie, Science & Technology, 32 Biomedical and clinical sciences, PREVENTION, Endocrinologie, ETIOLOGY, Médecine interne, Diabetes Mellitus, Type 1, ONSET, ANTIBODIES, Female, Life Sciences & Biomedicine
HLA CLASS-I, Male, GENETIC SUSCEPTIBILITY, Adolescent, ZINC TRANSPORTER-8, AUTOIMMUNITY, HLA-A24 Antigen, Endocrinology & Metabolism, Young Adult, Métabolisme, Belgian Diabetes Registry, Risk Factors, Humans, Genetic Predisposition to Disease, COMBINATION, Child, 11 Medical and Health Sciences, Original Research, Autoantibodies, RISK, Diabétologie, Science & Technology, 32 Biomedical and clinical sciences, PREVENTION, Endocrinologie, ETIOLOGY, Médecine interne, Diabetes Mellitus, Type 1, ONSET, ANTIBODIES, Female, Life Sciences & Biomedicine
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