Familial clustering of β-cell autoimmunity in initially non-diabetic children

Authors

  • Marika Kukko,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Medical School, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
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  • Anna Toivonen,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Medical School, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
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  • Antti Kupila,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Paediatrics, University of Turku, Turku, Finland
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  • Sari Korhonen,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Paediatrics, University of Oulu, Oulu, Finland
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  • Päivi Keskinen,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Medical School, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
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  • Riitta Veijola,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Paediatrics, University of Oulu, Oulu, Finland
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  • Suvi M. Virtanen,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Epidemiology and Health Promotion, National Institute of Public Health, Helsinki, Finland
    3. Tampere School of Public Health, University of Tampere, Finland
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  • Jorma Ilonen,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Virology, University of Turku, Turku, Finland
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  • Olli Simell,

    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Department of Paediatrics, University of Turku, Turku, Finland
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  • Mikael Knip

    Corresponding author
    1. JDRF Centre for the Prevention of Type 1 Diabetes in Finland
    2. Medical School, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
    3. Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
    • Hospital for Children and Adolescents, University of Helsinki, FIN-00029 HUCH, Helsinki, Finland.
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Abstract

Background

Type 1 diabetes is characterised by familial aggregation. We set out to explore whether β-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering.

Methods

Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A).

Results

Forty-four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (≥2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA-positive children within the same family was 3.3 years (range 0.0-10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0-3.2).

Conclusions

β-cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA-DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings. Copyright © 2005 John Wiley & Sons, Ltd.

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