Diagnostic Capabilities of Islet Autoantibodies in Children with New-Onset Type 1 Diabetes Mellitus and Healthy Siblings
The aim of the study is to determine the diagnostic utility of several islet autoantibodies and their combinations in order to identify individuals susceptible to type 1 diabetes mellitus (T1DM) among healthy siblings in the pediatric population within the scope of the development of a screening program.
Materials and Methods. A total of 424 children were evaluated, 260 children with new-onset T1DM and 164 healthy children with brothers and/or sisters with T1DM.
Blood tests for a complex of autoantibodies to insulin (IAA), tyrosine phosphatase (IA-2A), zinc transporter 8 (ZnT8A), pancreatic β-cells (ICA), and glutamate decarboxylase (GADA) were conducted in all the subjects with the enzyme immunoassay method.
Results. It was found that the diagnostic utility of individual autoantibodies is not equal and varies with age. The optimal age groups for the immunological control of the risks of developing type 1 diabetes in healthy siblings were determined. The highest risks were noted with the combination of GADA, ZnT8A, and IA-2A.
Conclusion. Islet autoantibodies may serve as prognostic markers of the risk of developing type 1 diabetes in healthy siblings.
- Couper J.J., Haller M.J., Greenbaum C.J., Ziegler A.G., Wherrett D.K., Knip M., Craig M.E. ISPAD Clinical Practice Consensus Guidelines 2018: stages of type 1 diabetes in children and adolescents. Pediatr Diabetes 2018; 19(Suppl 27): 20–27, https://doi.org/10.1111/pedi.12734.
- Vehik K., Lynch K.F., Schatz D.A., Akolkar B., Hagopian W., Rewers M., She J.X., Simell O., Toppari J., Ziegler A.G., Lernmark Å., Bonifacio E., Krischer J.P.; TEDDY Study Group. Reversion of β-cell autoimmunity changes risk of type 1 diabetes: TEDDY study. Diabetes Care 2016; 39(9): 1535–1542, https://doi.org/10.2337/dc16-0181.
- Bonifacio E. Predicting type 1 diabetes using biomarkers. Diabetes Care 2015; 38(6): 989–996, https://doi.org/10.2337/dc15-0101.
- Bosi E., Boulware D.C., Becker D.J., Buckner J.H., Geyer S., Gottlieb P.A., Henderson C., Kinderman A., Sosenko J.M., Steck A.K., Bingley P.J.; Type 1 Diabetes TrialNet Study Group. Impact of age and antibody type on progression from single to multiple autoantibodies in type 1 diabetes relatives. J Clin Endocrinol Metab 2017; 102(8): 2881–2886, https://doi.org/10.1210/jc.2017-00569.
- Gorus F.K., Balti E.V., Messaaoui A., Demeester S., Van Dalem A., Costa O., Dorchy H., Mathieu C., Van Gaal L., Keymeulen B., Pipeleers D.G., Weets I.; Belgian Diabetes Registry. Twenty-year progression rate to clinical onset according to autoantibody profile, age, and HLA-DQ genotype in a registry-based group of children and adults with a first-degree relative with type 1 diabetes. Diabetes Care 2017; 40(8): 1065–1072, https://doi.org/10.2337/dc16-2228.
- Regnell S.E., Lernmark Å. Early prediction of autoimmune (type 1) diabetes. Diabetologia 2017; 60(8): 1370–1381, https://doi.org/10.1007/s00125-017-4308-1.
- Steck A.K., Dong F., Waugh K., Frohnert B.I., Yu L., Norris J.M., Rewers M.J. Predictors of slow progression to diabetes in children with multiple islet autoantibodies. J Autoimmun 2016; 72: 113–117, https://doi.org/10.1016/j.jaut.2016.05.010.
- Endesfelder D., Hagen M., Winkler C., Haupt F., Zillmer S., Knopff A., Bonifacio E., Ziegler A.G., Zu Castell W., Achenbach P. A novel approach for the analysis of longitudinal profiles reveals delayed progression to type 1 diabetes in a subgroup of multiple-islet-autoantibody-positive children. Diabetologia 2016; 59(10): 2172–2180, https://doi.org/10.1007/s00125-016-4050-0.
- Garnier L., Marchand L., Benoit M., Nicolino M., Bendelac N., Wright C., Moulin P., Lombard C., Thivolet C., Fabien N. Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort. Clin Chim Acta 2018; 478: 162–165, https://doi.org/10.1016/j.cca.2017.12.043.
- Xu P., Krischer J.P.; Type 1 Diabetes TrialNet Study Group. Prognostic classification factors associated with development of multiple autoantibodies, dysglycemia, and type 1 diabetes — a recursive partitioning analysis. Diabetes Care 2016; 39(6): 1036–1044, https://doi.org/10.2337/dc15-2292.
- Gorus F.K., Balti E.V., Vermeulen I., Demeester S., Van Dalem A., Costa O., Dorchy H., Tenoutasse S., Mouraux T., De Block C., Gillard P., Decochez K., Wenzlau J.M., Hutton J.C., Pipeleers D.G., Weets I.; Belgian Diabetes Registry. Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients. Clin Exp Immunol 2013; 171(1): 82–90, https://doi.org/10.1111/j.1365-2249.2012.04675.x.
- Bingley P.J., Boulware D.C., Krischer J.P. Type 1 Diabetes TrialNet Study Group. The implications of autoantibodies to a single islet autoantigen to relatives with normal glucose tolerance. Diabetologia 2016; 59(3): 542–549, https://doi.org/10.1007/s00125-015-3830-2.
- Steck A.K., Vehik K., Bonifacio E., Lernmark A., Ziegler A.G., Hagopian W.A., She J., Simell O., Akolkar B., Krischer J., Schatz D., Rewers M.J.; TEDDY Study Group. Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care 2015; 38(5): 808–813, https://doi.org/10.2337/dc14-2426.
- Williams C.L., Long A.E. What has zinc transporter 8 autoimmunity taught us about type 1 diabetes? Diabetologia 2019; 62(11): 1969–1976, https://doi.org/10.1007/s00125-019-04975-x.