Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 148, Issue 1, Pages 72-78Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2249.2007.03334.x
Keywords
autoantibody epitopes; autoimmune; GAD65Ab; LADA
Categories
Funding
- NIDDK NIH HHS [DK026190, DK53456, DK53004, R01 DK026190, P01 DK053004, R01 DK053456] Funding Source: Medline
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We analysed the beta cell-specific autoimmunity reflected in autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab) in the prediabetic period of GAD65Ab-positive healthy adults who developed Type 2 diabetes (T2D) during a follow-up period of 10 years. We found that of the adults that tested GAD65Ab-positive at baseline (n = 25), six developed T2D and one developed Type 1 diabetes (T1D). Of the subjects that tested GAD65Ab-negative at baseline (n = 2209), 81 developed T2D, one developed T1D and four developed unclassified diabetes, indicating that the risk for GAD65Ab-positive healthy adults to develop diabetes is increased sixfold. The GAD65Ab epitopes were characterized in a competition radioligand binding assay using recombinant Fab derived of GAD65-specific monoclonal antibodies. We observed that the GAD65Ab epitope specificities in the prediabetic period changed dynamically. Specifically, the binding to a middle and a C-terminal epitope increased during the follow-up period (P = 0.03), causing a significant increase in the number of epitopes recognized (P = 0.03). These findings are similar to previous observations of dynamic changes in the prediabetic period of schoolchildren at high risk for T1D development. However, the character of the epitopes differs between the two populations, suggesting differences in the beta cell-specific autoimmune response in the prediabetic period of patients with latent autoimmune diabetes in adults (LADA) and T1D.
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