title: GAD autoantibody affinity in adult patients with latent autoimmune diabetes, the study participants of a GAD65 vaccination trial.
abstract: OBJECTIVE
  Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise β-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with β-cell function in participants of this trial.
  
  
  METHODS
  GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [125I]-labeled and unlabeled human GAD65.
  
  
  RESULTS
  At baseline, GADA affinities ranged from 1.9 × 10(7) to 5.0 × 10(12) L/mol (median 2.8 × 10(10) L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = -0.37; P = 0.01) and stimulated (r = -0.40; P = 0.006) C-peptide concentrations, and HbA1c (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (<4 × 10(9) L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01).
  
  
  CONCLUSIONS
  Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual β-cell function.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Krause
authors.affiliation: Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Landherr
authors.affiliation: Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.
authors.forename: Carl-David
authors.initials: CD
authors.lastname: Agardh
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Hausmann
authors.affiliation: Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Link
authors.affiliation: Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Hansen
authors.affiliation: Pediatrics Epidemiology Center, University of South Florida, Tampa, FL.
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Lynch
authors.affiliation: FIRS Laboratories, RSR Ltd., Cardiff, U.K.
authors.forename: Michael
authors.initials: M
authors.lastname: Powell
authors.affiliation: FIRS Laboratories, RSR Ltd., Cardiff, U.K.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Furmaniak
authors.affiliation: FIRS Laboratories, RSR Ltd., Cardiff, U.K.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rees-Smith
authors.affiliation: Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany.
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, GermanyForschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Anette G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, GermanyForschergruppe Diabetes e.V., Neuherberg, Germany peter.achenbach@helmholtz-muenchen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
mesh_terms: D000328:Adult; D000368:Aged; D000534:Alum Compounds / Q000737:chemistry; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000534:Alum Compounds; D001323:Autoantibodies; D002096:C-Peptide; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2