GAD65 autoantibody epitopes in adult patients with latent autoimmune diabetes following GAD65 vaccination


: Dr Christiane S. Hampe, Department of Medicine, Box 357710, University of Washington, Seattle, WA 98195, USA. E-mail:


Aims  Subcutaneous injection of recombinant human GAD65 (rhGAD65) in patients with latent autoimmune diabetes in adults (LADA) correlates with an increase in C-peptide levels. In this study we analysed the effect of rhGAD65 administration on the GAD65-specific autoimmune response.

Methods  Longitudinal serum samples obtained from LADA patients (n = 47) who received 4, 20, 100 or 500 µg alum-formulated rhGAD65 or placebo by subcutaneous injection twice (4 weeks apart) were analysed for their epitope recognition using GAD65-specific recombinant Fab and GAD65/67 fusion proteins.

Results  Overall, minor changes in the epitope pattern were observed using either approach. Only in the 500-µg dosage group was an increase in GAD65Ab level associated with a significant increase in the binding to a conformational epitope located at the middle part of GAD65.

Conclusions  Our data suggest that the apparent beneficial effects of 20 µg alum-formulated recombinant human GAD65 is not explained by changes in the GAD65Ab epitope pattern.