Evolution of islet autoantibodies in the Environmental Determinants of Islet Autoimmunity (ENDIA) prospective cohort
Date
2025
Authors
Couper, J.J.
Oakey, H.
Penno, M.A.S.
Wentworth, J.M.
Watson, K.
Brown, J.D.
Huynh, D.
Thomson, R.L.
Craig, M.E.
Davis, E.A.
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Diabetologia, 2025; 69(3):1-12
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Jennifer J. Couper, Helena Oakey, Megan A. S. Penno, John M. Wentworth, Kelly Watson, James D. Brown, Dao Huynh, Rebecca L. Thomson, Maria E. Craig, Elizabeth A. Davis, Aveni Haynes, Tony Huynh, Peter J. Vuillermin, Georgia Soldatos, Prudence E. Lopez, Grant Morahan, Kelly McGorm, Ki Wook Kim, Simon Barry, Emma E. Hamilton, Williams, William D. Rawlinson, Richard Sinnott, Leonard C. Harrison, Peter Achenbach, Peter G. Colman, on behalf of the ENDIA Study Group
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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 (χ2=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.
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© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025