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Diabetes. 2013 Apr;62(4):1345-50. doi: 10.2337/db12-0747. Epub 2012 Nov 16.

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

Collaborators (235)

Goubert P, Groven C, Baeten V, De Mesmaeker T, De Mesmaeker T, Dewinter H, Diependaele N, Exterbille S, Glorieux T, Haulet T, Ivens A, Kesler D, Lebleu F, Van Molle M, Vanderstraeten S, Verhaeghen K, Walgrave A, De Block G, Quartier E, Schoonjans G, Abrams P, Duvivier E, Maes W, Tshibuabua G, Arnouts P, Duyck F, Marchal M, T'sjoen G, Ayoubi S, Dysseleer A, Massa G, Tuyttens C, Bachy A, Eeckhout B, Massaad D, Unger J, Ballaux D, Emsens L, Mathieu C, Unuane D, Baltieri D, Engelen W, Matthijs Z, Van Acker K, Bataille G, Ers V, Maus Y, Van Aken S, Beckers V, Eykens A, Mekahli F, Van Crombrugge P, Beckers D, Favere N, Mekeirele K, Van de Poel G, Becq H, Fery F, Mertens A, Van Den Bruel A, Beirinckx J, Fils R, Messaaoui A, Van Doorn J, Beirinckx A, France A, Monballyu J, Van Gaal L, Bellavia S, Gaham N, Moorkens G, Van Gysegem D, Benhalima K, Garmyn K, Mortelmans K, Van Helvoirt M, Bex M, Gerard J, Mouraux T, Van Imschoot S, Bodson A, Gerniers S, Nachtegaele P, Van Parys C, Bosly F, Geronooz I, Naudts K, Van Pottelbergh I, Bouquegneau MS, Geyskens L, Nemery A, Van Poucke K, Bourguignon JP, Ghys Ch, Neven I, Van Rooy P, Carlier A, Gies I, Nicolaij D, Van Winghem C, Casteels K, Gillard P, Nobels F, Vanbesien J, Vanbesien J, Cavatorta E, Gillet C, Nollet A, Vande Mergel X, Chivu O, Giri M, Oriot P, Vandecauter H, Claessens A, Godon E, Ooms V, Vandemeulebroucke E, Claeys L, Gorus F, Oosterlynck C, Vandenbon C, Cnop M, Guiot J, Paciorkowski F, Vandenbroeck P, Coeckelberghs M, Haemers A, Paquot N, Vandenbroucke M, Col V, Haemers S, Paris I, Vandenbussche E, Colson A, Haumont S, Peeters G, Van Den Driessche A, Coolens JL, Herbaut Ch, Peiffer F, Vandergheynst A, Coremans P, Heyns E, Pelckmans C, Vanderijst JF, Crenier L, Huard A, Philips JC, Vanderijst M, Daems T, Hubermont G, Pieron M, Van der Schueren B, Damoiseaux P, Huyghe J, Pipeleers D, Vanderstappen H, Daoudi N, Immegeers V, Ponchon M, van Durme Y, Daper C, Jandrain B, Poschet K, Vanfleteren E, Daubresse C, Joosen P, Vanhaverbeke G, Daubresse JC, Jopart P, Remy C, Vanneste S, De Block C, Jousten E, Renneboog B, Vanuytsel J, De Brouckère V, Karmali R, Righes C, Verbiest R, Defacq L, Keymeulen B, Robbrecht S, Vercammen C, De Feyter I, Kleynen P, Rocour-Brumioul D, Verhaegen A, De Keyser L, Kockaerts Y, Rooman R, Verhaert G, De Schepper J, Krzentowski G, Ruige J, Verjans V, De Schynkel K, Laga K, Scarniere D, Verniest R, De Waele K, Lagasse E, Scheen A, Verschuere J, Decerf JA, Lamberigts G, Schils E, Vets B, Decochez K, Lambrecht E, Schoemaker I, Vieillevoye G, Decraene P, Lamkanfi F, Selvais P, Vinck W, Defoer F, Seret N, Vinckx J, Degrande E, Lemay P, Slap F, Vinken S, Den Brinker M, Lemy C, Spijker A, Warnotte C, De Paepe L, Leus J, Spincemaille K, Watillon P, Depoorter S, Lienart F, Stassen-Joly MP, Weber E.

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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