GAD65 autoantibody epitopes in adult patients with latent autoimmune diabetes following GAD65 vaccination.
OBJECTIVE
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.
Bekris
L M
LM
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Jensen
R A
RA
Lagerquist
E
E
Hall
T R
TR
Agardh
C-D
CD
Cilio
C M
CM
Lethagen
A L
AL
Lernmark
A
A
Robertson
J A
JA
Hampe
C S
CS
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014611:Vaccination
D001323:Autoantibodies; D000939:Epitopes; D005968:Glutamate Decarboxylase