title: Impact of intranasal insulin on insulin antibody affinity and isotypes in young children with HLA-conferred susceptibility to type 1 diabetes.
abstract: OBJECTIVE
  Despite promising results from studies on mouse models, intranasal insulin failed to prevent or delay the development of type 1 diabetes in autoantibody-positive children with HLA-conferred disease susceptibility. To analyze whether the insulin dose was inadequate to elicit an immunomodulatory response, we compared the changes observed in insulin antibody (IA) affinity and isotypes after treatment with nasal insulin or placebo.
  
  
  METHODS
  Ninety-five children (47 in the placebo group and 48 in the insulin group of the total of 224 children randomized for the trial) with HLA-conferred susceptibility to type 1 diabetes derived from the intervention arm of the Finnish Type 1 Diabetes Prediction and Prevention study were included in these analyses. Blood samples drawn before or at the beginning of the treatment and after treatment for 3 and 6 months were analyzed for IA affinity and isotype-specific IAs (IgG1-4, IgA, IgM, and IgE).
  
  
  RESULTS
  IgG3- and IgA-IA levels (P = 0.031 and 0.015, respectively) and the number of IgG3-IA-positive subjects (P = 0.022) were significantly higher at 6 months after the initiation of the treatment in the insulin group. No significant differences were observed between the two groups in IA affinity or other IA isotypes.
  
  
  CONCLUSIONS
  The insulin dose administered induced a modest change in the IA isotype profile. The lack of impact of nasal insulin on IA affinity implies that the immune response of study subjects was already mature at the beginning of the intervention.
authors.affiliation: Scientific Laboratory, Hospital for Children and Adolescents and Folkhälsan Research Center, University of Helsinki, Helsinki, Finland.
authors.forename: Samppa J
authors.initials: SJ
authors.lastname: Ryhänen
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Heli
authors.initials: H
authors.lastname: Siljander
authors.forename: Kirsti
authors.initials: K
authors.lastname: Näntö-Salonen
authors.forename: Tuula
authors.initials: T
authors.lastname: Simell
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D000281:Administration, Intranasal; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007330:Insulin Antibodies / Q000032:analysis / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007328:Insulin; D007330:Insulin Antibodies; D008562:Membrane Glycoproteins