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. Virtanen3,5,6,7,
- Jussi Lehtonen1,
- Jeffrey W. Almond4,
- Tuula Simell8,
- Olli Simell8,
- Jorma Ilonen9,10,
- Riitta Veijola11,
- Mikael Knip7,12,13,14 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, Tampere, Finland
- 6Nutrition Unit, Department of Lifestyle and Participation, National Institute for Health and Welfare, Helsinki, Finland
- 7Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 8Department of Pediatrics, Turku University Central Hospital, Turku, Finland
- 9Immunogenetics Laboratory, University of Turku, Turku, Finland
- 10Department of Clinical Microbiology, University of Eastern Finland, Kuopio Finland
- 11Institute of Clinical Medicine and Oulu University Hospital, Department of Pediatrics, University of Oulu, Oulu, Finland
- 12Folkhälsan Research Center, Helsinki, Finland
- 13Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
- 14Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland
- 15Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
- Corresponding author: Heikki Hyöty, .
O.H.L. and H.Ho. contributed equally to this work.
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 that 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 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0619/-/DC1.
- Received April 22, 2013.
- Accepted August 1, 2013.
- © 2014 by the American Diabetes Association.
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