title: Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin.
abstract: Enteral virus infections may trigger the development of beta-cell-specific autoimmunity by interacting with the gut-associated lymphoid system. We analyzed the effect of three different virus infections on immunization to dietary insulin in children carrying increased genetic risk for type 1 diabetes. Forty-six of 238 children developed multiple diabetes-associated autoantibodies and 31 clinical diabetes (median follow-up time 75 months). Insulin-binding antibodies were measured with EIA method (median follow-up time 24 months). Antibodies to enteroviruses, rotavirus and adenovirus were measured with EIA in samples drawn at birth and the ages of 3 and 6 months. Nineteen enterovirus, 14 rotavirus and 8 adenovirus infections were diagnosed. At the ages of 6, 12, and 18 months, the concentrations of insulin-binding antibodies were higher in children with postnatal entero-, rota- and/or adenovirus infections than in children without these infections. Children who subsequently developed ICA or IA-2 antibodies or clinical type 1 diabetes had higher concentrations of insulin-binding antibodies than children who remained autoantibody negative. Our data suggest that enteral virus infections can enhance immune response to insulin, induced primarily by bovine insulin in cow's milk. An enhanced antibody response to dietary insulin preceded the development of beta-cell specific autoimmunity and type 1 diabetes.
authors.affiliation: Immunogenetics Laboratory, University of Turku, Medicity, Biocity 4. krs, Tykistökatu 6 A, 20520 Turku, Finland. miia.makela@utu.fi
authors.forename: Miia
authors.initials: M
authors.lastname: Mäkelä
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Robert
authors.initials: R
authors.lastname: Hermann
authors.forename: Kimmo
authors.initials: K
authors.lastname: Salminen
authors.forename: Tero
authors.initials: T
authors.lastname: Vahlberg
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000821:virology; D019587:Dietary Supplements; D004198:Disease Susceptibility / Q000276:immunology / Q000821:virology*; D005767:Gastrointestinal Diseases / Q000150:complications / Q000821:virology; D006801:Humans; D007223:Infant; D007328:Insulin / Q000008:administration & dosage / Q000276:immunology*; D008892:Milk / Q000737:chemistry / Q000276:immunology; D014777:Virus Diseases / Q000150:complications*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D007328:Insulin