title: GAD autoantibody affinity in schoolchildren from the general population.
abstract: OBJECTIVE
  Subtyping GAD autoantibody (GADA) responses using affinity measurement allows the identification of GADA-positive children with a family history of type 1 diabetes who are at risk of developing diabetes. Here, we asked whether GADA affinity is a useful marker to stratify the risk of type 1 diabetes in GADA-positive schoolchildren from the general population.
  
  
  METHODS
  GADA affinity was measured by competitive binding experiments with [(125)I]-labelled and unlabelled human 65 kDa isoform of GAD (GAD65) in sera from 97 GADA-positive children identified in the Karlsburg Type 1 Diabetes Risk Study of a general schoolchild population in north-eastern Germany. GADA epitope specificity was determined using radiobinding assays with [(35)S]-labelled GAD65/67 kDa isoform of GAD (GAD67) chimeric proteins.
  
  
  RESULTS
  GADA affinity was high, ≥ 10(10) l/mol, in 33 of 35 multiple islet autoantibody-positive children. In contrast, the affinity ranged widely among 62 single GADA-positive children (median 3.1 × 10(9) l/mol; range 5.6 × 10(6) to >4.0 × 10(11) l/mol; p < 0.0001). High-affinity GADA were associated with HLA-DRB1*03 (p = 0.02) and predominantly directed against the C-terminal and/or middle part of the GAD65 protein. At follow-up, the affinity remained relatively constant. Five of the single GADA-positive children developed additional islet autoantibodies and had high-affinity GADA. Twenty-six children progressed to type 1 diabetes; among them, 23 had GADA affinities of ≥ 10(10) l/mol before disease onset.
  
  
  CONCLUSIONS
  Schoolchildren from the general population may develop heterogeneous GADA responses, and a high affinity can identify those GADA-positive children who are more likely to progress to type 1 diabetes.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurt am Main, Germany, bender@med.uni-frankfurt.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Bender
authors.forename: Michael
authors.initials: M
authors.lastname: Schlosser
authors.forename: Urs
authors.initials: U
authors.lastname: Christen
authors.forename: Anette G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D008297:Male
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2