title: Autoantibodies to GAD, IA-2 and insulin in ICA-positive first-degree relatives of children with type 1 diabetes: a comparison between parents and siblings.
abstract: BACKGROUND
  Islet cell antibodies (ICA) represent a heterogenous group of autoantibodies to diabetes-associated antigens, including glutamic acid decarboxylase (GAD) and the IA-2 protein. The objectives of the present study were to compare the prevalence of autoantibodies to known biochemically characterized autoantigens between ICA-positive non-diabetic parents and siblings of children with type 1 diabetes and to evaluate how such antibodies explain ICA reactivity.
  
  
  METHODS
  The presence and levels of GAD antibodies (GADA), IA-2 antibodies (IA-2A) and insulin autoantibodies (IAA) were analyzed in the sera of 184 ICA-positive first-degree relatives (79 parents and 105 siblings).
  
  
  RESULTS
  The prevalences of GADA (61.9% in siblings vs 32.9% in parents), IA-2A (55.2% vs 15.2%) and IAA (41.0% vs 0%) were increased among ICA-positive siblings relative to ICA-positive parents (p<0.001). The siblings had higher ICA titers (p<0.001) than the parents but tended to have lower GADA levels (p=0.12). IA-2A levels did not differ between the two groups. IA-2A levels explained a higher proportion of the ICA reactivity in the siblings than in the parents (44% vs 12%, p=0.004), and GADA levels had the same tendency (27% vs 10%, p=0.11). In a multiple regression analysis, GADA and IA-2A were found to explain together 16% of the ICA reactivity in parents and 49% in siblings (p=0.003 for the difference).
  
  
  CONCLUSIONS
  These results indicate that the increased frequency of additional diabetes-associated autoantibodies in ICA-positive siblings when compared to their ICA-positive parents may reflect the increased risk of progression to clinical type 1 diabetes previously reported in young ICA-positive relatives. We conclude that ICA immunofluorescence is not only due to GADA and IA-2A, but there are other additional antigens contributing to the ICA reactivity. Antibodies to such antigens appear to be more common among adults than in children.
authors.affiliation: Department of Pediatrics, University of Oulu, Oulu, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Korhonen
authors.forename: Maria M
authors.initials: MM
authors.lastname: Knip
authors.forename: Petri
authors.initials: P
authors.lastname: Kulmala
authors.forename: Kaisa
authors.initials: K
authors.lastname: Savola
authors.forename: Hans K
authors.initials: HK
authors.lastname: Akerblom
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D007328:Insulin / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D009679:Nuclear Family; D010290:Parents; D012044:Regression Analysis
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D007328:Insulin; D005968:Glutamate Decarboxylase