University of Oulu

Petra M Pöllänen, Samppa J Ryhänen, Jorma Toppari, Jorma Ilonen, Paula Vähäsalo, Riitta Veijola, Heli Siljander, Mikael Knip, Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 12, December 2020, Pages e4638–e4651,

Dynamics of islet autoantibodies during prospective follow-up from birth to age 15 years

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Author: Pöllänen, Petra M.1,2; Ryhänen, Samppa J.1; Toppari, Jorma3;
Organizations: 1Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Department of Pediatrics, Turku University Hospital, and Institute of Biomedicine and Centre for Population Health Research, University of Turku, Turku, Finland
4Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland
5Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
6Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
7Folkhälsan Research Center, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Endocrine society, 2020
Publish Date: 2021-01-22


Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context.

Design: HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9–15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D.

Results: By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3–15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A– and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01).

Conclusions: In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.

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Series: Journal of clinical endocrinology & metabolism
ISSN: 0021-972X
ISSN-E: 1945-7197
ISSN-L: 0021-972X
Volume: 105
Issue: 12
Pages: 1 - 14
DOI: 10.1210/clinem/dgaa624
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the JDRF (grants 1-SRA-2016-342-M-R, 1-SRA-2019-732-M-B); European Union (grant BMH4-CT98-3314); Novo Nordisk Foundation; Academy of Finland (Decision No 292538 and Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017, Decision No. 250114); Special Research Funds for University Hospitals in Finland; Diabetes Research Foundation, Finland; Sigrid Juselius Foundation, Finland; Finska Läkaresällskapet, Finland; Maud Kuistila Memorial Foundation, Finland; Yrjö Jahnsson Foundation, Finland; Biomedicum Helsinki Foundation, Finland; Orion Research Foundation sr, Finland; and the Pediatric Research Foundation, Finland.
Copyright information: © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.