title: GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes.
abstract: OBJECTIVE
  We have previously shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by increased GAD autoantibody (GADA) titers. The aim of this study was to investigate whether GAD-alum treatment affected the GADA epitope pattern.
  
  
  METHODS
  Serum samples from patients treated with GAD-alum (n = 33) or placebo (n = 27), at baseline, 1, 3, 9, and 15 months after the initial injection, were tested for their binding capacity to specific GADA epitopes in an epitope-specific radioligand binding assay with six recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78, and N-GAD(65) mAb).
  
  
  RESULTS
  No significant differences in variability of binding to any of the tested rFab were observed from baseline to 15 months. There was a sustained low binding of GADA to the b78- and N-GAD(65) mAb-defined epitopes, often recognized by GADA in patients with stiff person syndrome (SPS) and seldom in T1D patients. However, binding of GADA to the T1D-associated b96.11-defined epitope increased between baseline and 3 months in GAD-alum (-8.1%, min -72.4%, max 39.6%) compared to placebo patients (1.5%, min -28.3%, max 28.6%) (p = 0.02). Subsequently, the b96.11-defined epitope recognition returned to levels similar to that observed at baseline.
  
  
  CONCLUSIONS
  GAD-alum injections did not affect binding of GADA to SPS-related epitopes, further supporting the safety of the treatment. There were no changes in GADA epitope specificity to the T1D-related epitopes, except for a temporarily increased binding to one of the tested epitopes.
authors.affiliation: Division of Pediatrics & Diabetes Research Centre, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. camilla.skoglund@liu.se
authors.forename: Camilla
authors.initials: C
authors.lastname: Skoglund
authors.forename: Mikael
authors.initials: M
authors.lastname: Chéramy
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
mesh_terms: D000293:Adolescent; D000534:Alum Compounds / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans
chemical_list: D000534:Alum Compounds; D001323:Autoantibodies; D000939:Epitopes; C041524:aluminum sulfate; D005968:Glutamate Decarboxylase