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Åke Lernmark

Principal investigator

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GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

Author

  • Stephanie Krause
  • Ulrike Landherr
  • Carl-David Agardh
  • Simone Hausmann
  • Katarina Link
  • Jesse M. Hansen
  • Kristian F. Lynch
  • Michael Powell
  • Jadwiga Furmaniak
  • Bernard Rees-Smith
  • Ezio Bonifacio
  • Anette G. Ziegler
  • Åke Lernmark
  • Peter Achenbach

Summary, in English

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 beta-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 beta-cell function in participants of this trial. RESEARCH DESIGN AND 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 [I-125]-labeled and unlabeled human GAD65. RESULTS At baseline, GADA affinities ranged from 1.9 X 10(7) to 5.0 X 10(12) L/mol (median 2.8 X 10(19) 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 HbA(1c) (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 X 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 beta-cell function.

Department/s

  • Department of Clinical Sciences, Malmö
  • Diabetes - Clinical Obesity
  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2014

Language

English

Pages

1675-1680

Publication/Series

Diabetes Care

Volume

37

Issue

6

Document type

Journal article

Publisher

American Diabetes Association

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Clinical Obesity
  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1935-5548