Evolution of islet autoantibodies in the Environmental Determinants of Islet Autoimmunity (ENDIA) prospective cohort
- Author(s)
- Couper, JJ; Oakey, H; Penno, MAS; Wentworth, JM; Watson, K; Brown, JD; Huynh, D; Thomson, RL; Craig, ME; Davis, EA; Haynes, A; Huynh, T; Vuillermin, PJ; Soldatos, G; Lopez, PE; Morahan, G; McGorm, K; Kim, KW; Barry, S; Hamilton-Williams, EE; Rawlinson, WD; Sinnott, R; Harrison, LC; Achenbach, P; Colman, PG;
- Journal Title
- Diabetologia
- Publication Type
- Dec 11
- Abstract
- AIMS/HYPOTHESIS: Islet autoantibodies herald early type 1 diabetes. However, less is known of the evolution of autoantibodies to the islet autoantigen ZnT8. Our primary aim was to characterise the development of islet autoantibodies in a pregnancy-birth at-risk cohort and to provide new knowledge about ZnT8A. METHODS: Islet autoantibodies were measured every 3-6 months in 1277/1473 children with a first-degree relative with type 1 diabetes who were followed prospectively from pregnancy in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort for 7.0 (IQR 5.8-8.3) years. Islet autoantibodies were also measured in the mothers and/or in cord blood in 901 pregnancies with type 1 diabetes. RESULTS: The development of persistent IAA reached a probability of 0.02 by 2 years of age. A combination of IAA- and GADA-first, GADA-first and ZnT8A-first all reached a similar probability by 5 years of age. ZnT8A appeared as the first islet autoantibody, alone or in combination, in 43 (32%) of the 134/1473 children with persistent islet autoantibodies. Persistent single ZnT8A, detected only by ELISA, usually appeared after 4 years of age. ZnT8A that progressed to multiple islet autoantibodies or type 1 diabetes were detected in younger children (p=0.006) and in multiple assay formats. ZnT8A were confirmed in additional assay formats when present with multiple islet autoantibodies, but not when remaining as a single islet autoantibody, unlike IAA and GADA. Maternal islet GADA were detected until 15 months of age and transmission of any islet antibody/autoantibody did not relate to islet autoantibody development in the offspring (χ(2)=3.32, df=2, p=0.19). CONCLUSIONS/INTERPRETATION: Persistent single ZnT8A, which are detected only by ELISA and no other test format, appear not to confer an increased risk of progression to type 1 diabetes.
- Publisher
- Springer Nature
- Keywords
- Children; Islet autoantibodies; Type 1 diabetes; ZnT8 (zinc transporter 8)
- Research Division(s)
- Immunology
- PubMed ID
- 41379147
- Publisher's Version
- https://doi.org/10.1007/s00125-025-06591-4
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-12-15 09:44:04
Last Modified: 2025-12-15 09:44:10