Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin

Enteral virus infections may trigger the development of β-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 β-cell specific autoimmunity and type 1 diabetes. © 2006 Elsevier Ltd. All rights reserved.

Vaarala, Outi,1962-Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Pediatrik,Barn- och ungdomskliniken i Linköping(Swepub:liu)outva41 (author)
Hermann, RobertImmunogenomics Lab, Cell Screen Applied Biomedi cal Res Center, Budapest. Hungary (author)
Salminen, KimmoDept of Virology, Turku, Finland (author)
Vahlberg, TeroDept of Biostatistics University of Turku, Finland (author)
Veijola, RiitaDept of Pediatrics, University of Oulu, Finland (author)
Hyöty, HeikkiDept of Virology, University of Tampere, Finland (author)
Knip, MikaelHospital for Children and Adolescents, University of Helsinki, Finland (author)
Simell, OlliImmunogenetics Lab, University of Turku, Finland (author)
Ilonen, JormaDept of Clin Microbiology, University of Kuopio, Finland (author)
Immunogenetics Lab, University of Turku, FinlandHälsouniversitetet (creator_code:org_t)

By the author/editor: Mäkelä, Miia; Vaarala, Outi, 1 ...; Hermann, Robert; Salminen, Kimmo; Vahlberg, Tero; Veijola, Riita; show more...; Hyöty, Heikki; Knip, Mikael; Simell, Olli; Ilonen, Jorma; show less...

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