Details

Autor(en) / Beteiligte

• MBUNWE, Eric
• VAN DER AUWERA, Bart J
• VAN SCHRAVENDIJK, Chris
• WENZLAU, Janet M
• HUTTON, John C
• PIPELEERS, Daniel
• WEETS, Ilse
• GORUS, Frans K
• VERMEULEN, Ilse
• DEMEESTER, Simke
• VAN DALEM, Annelien
• BALTI, Eric V
• VAN AKEN, Sara
• DERDELINCKX, Luc
• DORCHY, Harry
• DE SCHEPPER, Jean

Titel

HLA-A24 Is an Independent Predictor of 5-Year Progression to Diabetes in Autoantibody-Positive First-Degree Relatives of Type 1 Diabetic Patients

Ist Teil von

• Diabetes (New York, N.Y.), 2013-04, Vol.62 (4), p.1345-1350

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.