title: Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies.
abstract: OBJECTIVE
  The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A).
  
  
  METHODS
  A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q).
  
  
  RESULTS
  An isolated positivity for ICA was identified in 5.0% (17/341) of the newly diagnosed children. The levels of ICA in positive subjects ranged from 3 to 183 JDF-U (median 30). This finding increased the diagnostic sensitivity of islet autoimmunity as 3204/3545 patients (90.4%) were islet autoantibody positive without the ICA analyses and 3221 patients (90.9%) were positive with the inclusion of ICA.
  
  
  CONCLUSIONS
  The finding of an isolated positivity for ICA despite negativity for GADA, IA-2A, IAA, and ZnT8A (R, W, Q) suggests that still another yet unidentified autoantigen(s) may contribute to the ICA immunofluorescence. Hence, ICA is important to analyze in type 1 diabetes children and adolescents that would otherwise be islet autoantibody negative.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Andersson
authors.forename: Martin
authors.initials: M
authors.lastname: Kolmodin
authors.forename: Sten-Anders
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: Annelie
authors.initials: A
authors.lastname: Carlsson
authors.forename: Gun
authors.initials: G
authors.lastname: Forsander
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindblad
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Claude
authors.initials: C
authors.lastname: Marcus
authors.forename: Ulf
authors.initials: U
authors.lastname: Samuelsson
authors.forename: Eva
authors.initials: E
authors.lastname: Ortqvist
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Helena
authors.initials: H
authors.lastname: Elding Larsson
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D013548:Sweden
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; C024211:islet cell antibody; D005968:Glutamate Decarboxylase
keywords: autoantigens; diagnostic sensitivity; type 1 diabetes mellitus