title: Interaction of enterovirus infection and cow's milk-based formula nutrition in type 1 diabetes-associated autoimmunity.
abstract: BACKGROUND
  Enteral virus infections and early introduction of cow's milk (CM)-based formula are among the suggested triggers of type 1 diabetes (T1D)-associated autoimmunity, although studies on their role have remained contradictory. Here, we aimed to analyse whether interactions between these factors might clarify the controversies.
  
  
  METHODS
  The study population comprised 107 subjects developing positivity for at least two T1D-associated autoantibodies and 446 control subjects from the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus, adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies were analysed from prospective serum samples at 3-24 months of age. Data on infant cow's milk exposure were available for 472 subjects: 251 subjects were exposed to cow's milk before 3 months of age and 221 subjects later in infancy.
  
  
  RESULTS
  Signs of an enterovirus infection by 12 months of age were associated with the appearance of autoimmunity among children who were exposed to cow's milk before 3 months of age. Cox regression analysis revealed a combined effect of enterovirus infection and early cow's milk exposure for the development of ICA and any of the biochemically defined autoantibodies (p = 0.001), of IAA (p = 0.002), GADA (p = 0.001) and IA-2A (p = 0.013).
  
  
  CONCLUSIONS
  The effect of enterovirus infection on the appearance of T1D-associated autoimmunity seems to be modified by exposure to cow's milk in early infancy suggesting an interaction between these factors. Moreover, these results provide an explanation for the controversial findings obtained when analysing the effect of any single one of these factors on the appearance of T1D-associated autoimmunity.
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland. johanna.lempainen@utu.fi
authors.forename: J
authors.initials: J
authors.lastname: Lempainen
authors.forename: S
authors.initials: S
authors.lastname: Tauriainen
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
authors.forename: M
authors.initials: M
authors.lastname: Mäkelä
authors.forename: H
authors.initials: H
authors.lastname: Honkanen
authors.forename: J
authors.initials: J
authors.lastname: Marttila
authors.forename: R
authors.initials: R
authors.lastname: Veijola
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.forename: H
authors.initials: H
authors.lastname: Hyöty
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity / Q000235:genetics*; D002417:Cattle; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004769:Enterovirus Infections / Q000150:complications* / Q000276:immunology; D005387:Finland; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007225:Infant Food; D007330:Insulin Antibodies / Q000032:analysis; D008892:Milk / Q000276:immunology*; D011446:Prospective Studies; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012401:Rotavirus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D007330:Insulin Antibodies; D005968:Glutamate Decarboxylase