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 microg 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-microg 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 microg alum-formulated recombinant human GAD65 is not explained by changes in the GAD65Ab epitope pattern.
AIMS: Subcutaneous injection of recombinant humanGAD65 (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 microg 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-microg 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 microg alum-formulated recombinant humanGAD65 is not explained by changes in the GAD65Ab epitope pattern.
Authors: E Ortqvist; B Brooks-Worrell; K Lynch; J Radtke; L M Bekris; I Kockum; C-D Agardh; C M Cilio; A L Lethagen; B Persson; A Lernmark; J Reichow; S Oak; J P Palmer; C S Hampe Journal: J Clin Endocrinol Metab Date: 2010-08-04 Impact factor: 5.958