Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes
- Olli H. Laitinen1,†,
- Hanna Honkanen2,†,
- Outi Pakkanen1,
- Sami Oikarinen2,
- Minna M Hankaniemi1,
- Heini Huhtala3,
- Tanja Ruokoranta1,
- Valérie Lecouturier4,
- Philippe André4,
- Raimo Harju1,
- Suvi M. Virtanen3,5,6,14,
- Jussi Lehtonen1,
- Jeffrey W. Almond4,
- Tuula Simell7,
- Olli Simell7,
- Jorma Ilonen8,9,
- Riitta Veijola10,
- Mikael Knip11,12,13,14 and
- Heikki Hyöty2,*,15
- 1Vactech Ltd, Tampere, Finland
- 2Department of Virology, School of Medicine, University of Tampere, Tampere, Finland
- 3School of Health Sciences, University of Tampere, Tampere, Finland
- 4Sanofi-Pasteur, Marcy L’Etoile, France
- 5The Science Center of Pirkanmaa Hospital District, Finland
- 6Nutrition Unit, Department of Lifestyle and Participation, National Institute for Health and Welfare, Helsinki, Finland
- 7Department of Pediatrics, Turku University Central Hospital, Turku, Finland
- 8Immunogenetics Laboratory, University of Turku, Turku, Finland
- 9Department of Clinical Microbiology, University of Eastern Finland, Kuopio Finland
- 10Institute of Clinical Medicine and Oulu University Hospital, Department of Pediatrics, University of Oulu, Oulu, Finland
- 11Folkhälsan Research Center, Helsinki, Finland
- 12Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
- 13Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland
- 14Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 15Department of Clinical Microbiology, Center for Laboratory Medicine, Tampere, Finland
- *Corresponding author: Heikki Hyöty, E-mail:
† These authors contributed equally to this work. The first two authors wrote the initial draft of the manuscript; all the authors contributed to the final version of the manuscript and vouch for the accuracy and completeness of the reported data.
The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes which could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and it was attenuated by the presence of maternal antibodies against the virus. Two other Coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern suggesting immunological cross-protection against Coxsackievirus B1. These results support previous observations suggesting that the group B Coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.
- Received April 22, 2013.
- Accepted July 31, 2013.
- © 2013 by the American Diabetes Association.
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