Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: A prospective study

Authors

  • M. Lönnrot,

    Corresponding author
    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Virology, University of Tampere, Medical School and Tampere University Hospital, Tampere, Finland
    • University of Tampere, Medical School, Department of Virology, P.O. Box 607, FIN- 33101 Tampere, Finland
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  • K. Salminen,

    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Virology, University of Turku, Turku, Finland
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  • M. Knip,

    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Pediatrics, University of Tampere, Medical School and Tampere University Hospital, Tampere, Finland
    3. Department of Pediatrics, University of Oulu, Oulu, Finland
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  • K. Savola,

    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Pediatrics, University of Oulu, Oulu, Finland
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  • P. Kulmala,

    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Pediatrics, University of Oulu, Oulu, Finland
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  • P. Leinikki,

    1. National Public Health Institute, Helsinki, Finland
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  • T. Hyypiä,

    1. Haartman Institute, University of Helsinki, Helsinki, Finland
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  • H.K. Åkerblom,

    1. Children's Hospital, University of Helsinki, Helsinki, Finland
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  • H. Hyöty

    1. JDFI Center for Prevention of Type 1 Diabetes in Finland, Tampere, Finland
    2. Department of Virology, University of Tampere, Medical School and Tampere University Hospital, Tampere, Finland
    3. Department of Virology, University of Turku, Turku, Finland
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Abstract

Recent prospective studies have documented serologically an increased frequency of enterovirus infections in prediabetic children, indicating that these infections may initiate and accelerate the beta-cell damaging process several years before the clinical manifestation of type 1 diabetes. The aim of the present study was to establish whether these serological findings would be supported by the detection of enterovirus RNA in a unique prospective series of sera collected from prediabetic children 0–10 years before the manifestation of clinical type 1 diabetes. Reverse transcription followed by polymerase chain reaction employing highly conserved primers among enteroviruses were used to amplify enteroviral sequences. Viral RNA was found in 22% (11/49) of follow-up samples from prediabetic children but in only 2% (2/105) of those from controls (OR 14.9, P < 0.001). Persisting RNA positivity was not observed in any of these children. The presence of enterovirus RNA was associated with concomitant increases in the levels of autoantibodies against islet cells (OR 21.7, P < 0.01) and glutamic acid decarboxylase (OR 15.4, P < 0.05), but not in the levels of antibodies against insulin or the tyrosine phosphatase-like IA-2 protein. In contrast to the prediabetic children, those with newly diagnosed type 1 diabetes were negative for enterovirus RNA. The results thus complement previous serological data, suggesting that enterovirus infections are an important risk factor underlying type 1 diabetes and associated with the induction of beta-cell autoimmunity even years before symptoms appear. J. Med. Virol. 61:214–220, 2000. © 2000 Wiley-Liss, Inc.

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