Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood

Witold Bauer, Riitta Veijola, Johanna Lempainen, Minna Kiviniemi, Taina Härkönen, Jorma Toppari, Mikael Knip, Attila Gyenesei, Jorma Ilonen

    Research output: Contribution to journalArticleScientificpeer-review

    28 Citations (Scopus)

    Abstract

    Context: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. Objective: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. Design and methods: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. Results: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. Conclusions: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.

    Original languageEnglish
    Pages (from-to)4521-4530
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume104
    Issue number10
    DOIs
    Publication statusPublished - 2019
    Publication typeA1 Journal article-refereed

    Funding

    Financial Support: The Type 1 Diabetes Prediction and Prevention study was funded by the Juvenile Diabetes Research Foundation Grant 1-SRA-2016-342-M-R (R.V.); the Academy of Finland Grant 286765 (J.I.); the Sigrid Jusélius Foundation (J.I.); and Special Research Funds for Tampere, Turku, and Oulu University Hospitals (M.K.). W.B. was supported by the CIR Poland Grant KNOW/2012-2017.

    Publication forum classification

    • Publication forum level 2

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Biochemistry
    • Endocrinology
    • Clinical Biochemistry
    • Biochemistry, medical

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