Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Coxsackievirus B1 is associated with type 1 diabetes – results from virus antibody survey in different European populations (#88)

Amirbabak Sioofy Khojine 1 , Sami Oikarinen 1 , Didier Hober 2 , Bernadette Lucas 2 , Andriani Vazeou 3 , Dalia Marciulionyte 4 , Vallo Tillman 5 , Kaire Heilman 5 , Raivo Uibo 5 , Evangelos Bozas 3 , Peter Muir 6 , hanna Honkanen 1 , Steven M Oberste 7 , Jorma Ilonen 8 , Mikael Knip 9 , Päivi Keskinen 10 , Marja-Terttu Saha 10 , Heini Huhtala 1 , Glyn Stanway 11 , Christos Bartsocas 3 , Johnny Ludvigsson 12 , Heikki Hyoty 1
  1. University of Tampere, Tampere, Finland
  2. University Lille and CHR, Lille, France
  3. 3National University of Athens, Athens, Greece
  4. Kaunas University of Medicine, Kaunas, Lithuania
  5. University of Tartu, Tartu, Estonia
  6. Public Health England, Bristol, UK
  7. Centers for Disease Control and Prevention, Atlanta, US
  8. University of Turku, Turku, Finland
  9. Children Hospital, University of Helsinki, Helsinki, Finland
  10. Tampere University Hospital, Tampere, Finland
  11. University of Essex, Colchester, UK
  12. Linköping University, Linköping, Sweden

Background

Enteroviruses have been connected to type 1 diabetes (T1D) in various studies. Our recent observations in different populations suggest that this association may be linked to specific enterovirus types, such as coxsackievirus B1 (CBV1). Now we expanded these studies by increasing the size of previous cohorts and adding new populations to screen neutralizing antibodies against a wide panel of different CBV1 strains in patients with newly diagnosed T1D and matched controls. The presence of such antibodies is a highly specific indicator of past CBV1 infection.

Subjects and methods

The study cohort included 340 children with newly diagnosed T1D and 340 matched controls recruited in England, Estonia, Finland, France, Greece, Lithuania and Sweden during the years 2001-2007 in the EU-funded VirDiab study.  One control child was selected for each case child and matched for the sampling time, gender and country. Neutralizing antibodies were analysed from serum against 11 different wild-type CBV1 strains and one prototype CBV1 strain using a plaque assay. Presence of antibodies against at least one of these strains was taken as an indicator or past infection.

Results

 CBV1 antibodies were more frequent among diabetic children than in control children. Altogether 48 % of the case children and 38 % of the control children had antibodies against at least one of the CBV1 strains (OR=1.7, 95% CI 1.2-2.4; p=0.003). CBV1-associated risk was not related to HLA genotype, age or gender. Finnish children had a lower frequency of CBV1 antibodies than children in other countries (22% vs. 52%, p<0.001).

Conclusion

The results support previous studies confirming a risk association between CBV1 infections and T1D. This finding opens up new possibilities to study the mechanisms of enterovirus-induced beta-cell damage and explore the options to prevent T1D by a virus vaccine.

Funded by EU and the Academy of Finland