title: Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children.
abstract: OBJECTIVE
  We evaluated the role of enterovirus infections in the pathogenesis of Type I (insulin-dependent) diabetes mellitus by monitoring enterovirus antibody levels in prediabetic children who turned positive for diabetes-associated autoantibodies in a prospective birth cohort study.
  
  
  METHODS
  Serial serum samples taken during prospective observation starting at birth were analysed for IgG and IgA class antibodies against enterovirus antigens including purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic enterovirus peptide antigen using enzyme immunoassay. Maternal samples taken at the end of the third month of pregnancy were also studied. Analyses were done from 21 childen who developed autoantibodies and from 104 autoantibody-negative control children who were matched for the time of birth, gender and HLA susceptibility alleles. For comparison, adenovirus antibodies were also analysed from all samples collected.
  
  
  RESULTS
  IgG class enterovirus antibody levels were high in maternal samples and in cord blood in both case and control children. After birth the IgG levels decreased reaching a nadir at the age of 6 months. No IgA class antibodies were detected at birth but started to emerge postnatally. Antibody levels did not differ between the autoantibody positive and the control children during the first 6 months of life. From 6 months to 24 months of age, the autoantibody positive children had higher IgG and IgA levels against coxsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigens than control children but poliovirus 1 and adenovirus antibodies were closely similar in the two groups. The difference between children with autoantibodies and control children was predominantly seen among boys and among those with the HLA-DQB1*0302/x genotype.
  
  
  CONCLUSIONS
  Our data show that children who seroconverted for diabetes-associated auto-antibodies develop stronger humoral immune responses to coxsackievirus B4, echovirus 11 and a synthetic enterovirus peptide antigen than children who remained negative for autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not differ between the prediabetic and control children suggesting that the regulation of antibody responses to enteroviruses is not disturbed. Accordingly, the results imply a stronger enterovirus exposure in prediabetic children supporting the role of enteroviruses in the pathogenesis of Type I diabetes.
authors.affiliation: Department of Virology, University of Tampere and Tampere University Hospital, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Sadeharju
authors.forename: M
authors.initials: M
authors.lastname: Lönnrot
authors.forename: T
authors.initials: T
authors.lastname: Kimpimäki
authors.forename: K
authors.initials: K
authors.lastname: Savola
authors.forename: S
authors.initials: S
authors.lastname: Erkkilä
authors.forename: T
authors.initials: T
authors.lastname: Kalliokoski
authors.forename: P
authors.initials: P
authors.lastname: Savolainen
authors.forename: P
authors.initials: P
authors.lastname: Koskela
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.forename: H
authors.initials: H
authors.lastname: Hyöty
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D004769:Enterovirus Infections / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D011236:Prediabetic State / Q000276:immunology*; D012307:Risk Factors
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C024211:islet cell antibody