title: Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study.
abstract: Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes-associated HLA-DQB1 alleles, and those with an increased genetic risk are invited for prospective follow-up. Enterovirus infections were diagnosed by serology and reverse transcriptase-polymerase chain reaction (RT-PCR) from serum samples taken from birth every 3-6 months. Case children included 41 infants who became positive for diabetes-associated autoantibodies during the observation. Control children comprised altogether 196 infants who remained autoantibody negative and were matched for the time of birth, sex, and HLA-DQB1 alleles. Enterovirus infections were more frequent in case children than in control children (P = 0.004), and the average enterovirus antibody levels were also higher in the case children (P = 0.003). Enterovirus infections were particularly frequent during the 6-month period preceding the first detection of autoantibodies: 51% of the case children compared with 28% of the control children had an infection in that time interval (P = 0.003). There was no difference in the frequency of adenovirus infections between the groups (P = 0.9). The present results imply that enterovirus infections are associated with the appearance of beta-cell autoantibodies. A possible causal relationship is supported by the clustering of infections to the time when autoantibodies appeared.
authors.affiliation: Juvenile Diabetes Research Foundation Center for Prevention of Type 1 Diabetes in Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Salminen
authors.forename: Karita
authors.initials: K
authors.lastname: Sadeharju
authors.forename: Maria
authors.initials: M
authors.lastname: Lönnrot
authors.forename: Paula
authors.initials: P
authors.lastname: Vähäsalo
authors.forename: Antti
authors.initials: A
authors.lastname: Kupila
authors.forename: Sari
authors.initials: S
authors.lastname: Korhonen
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
mesh_terms: D000257:Adenoviridae Infections / Q000276:immunology* / Q000821:virology; D000914:Antibodies, Viral / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D004769:Enterovirus Infections / Q000150:complications* / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G