HIGH TITERS OF AUTOANTIBODIES TO GLUTAMATE DECARBOXYLASE IN TYPE 1 DIABETES PATIENTS : EPITOPE ANALYSIS AND INHIBITION OF ENZYME ACTIVITY

Objective: Autoantibodies to glutamate decarboxylase (GAD65Ab) are found in patients with autoimmune neurological disorders or type 1 diabetes. The correct diagnosis of GAD65Ab-associated neurological disorders is often delayed by the variability of symptoms and a lack of diagnostic markers. We hypothesized that the frequency of neurological disorders with high GAD65Ab titers is significantly higher than currently recognized.
Methods: We analyzed GAD65Ab titer, GAD65 enzyme activity inhibition, and GAD65Ab epitope pattern in a cohort of type 1 diabetes patients (n = 100) and correlated our findings with neurological symptoms and diseases.
Results: Overall, 43% (43/100) of patients had detectable GAD65Ab titers (median = 400 U/mL, range: 142-250,000 U/mL). The GAD65Ab titers in 10 type 1 diabetes patients exceeded the 90th percentile of the cohort (2,000-250,000 U/mL). Sera of these 10 patients were analyzed for their GAD65Ab epitope specificity and their ability to inhibit GAD65 enzyme activity in vitro. GAD65Ab of 5 patients inhibited the enzyme activity significantly (by 34-55%). Three patients complained of muscle stiffness and pain, which was documented in 2 of these patients. 
Conclusions: Based on our findings, we suggest that neurological disorders with high GAD65Ab titers are more frequent in type 1 diabetes patients than currently recognized. (Endocr Pract. 2013;19:663-668) © 2013 AACE.