GAD65 autoantibodies (GAD65Ab) are important markers for type 1 (insulin-de
pendent) diabetes mellitus. Although most patients have GAD65Ab at the time
of clinical diagnosis, there are also GAD65Ab-positive individuals in the
population at low risk of developing type 1 diabetes. The aim of this study
was to test the hypothesis that the GAD65Ab reactivity to GAD65 cloned fro
m human, mouse, and rat in newly diagnosed type 1 diabetic patients differ
from antibody-positive healthy individuals. Sera from 254 new-onset 0- to 3
4-yr-old type 1 diabetic patients and 270 controls were assayed for their r
eactivity to human, mouse, and rat GAD65. Among the type 1 diabetic patient
s there was a significant better binding of human GAD65 compared to either
mouse (P = 0.03) or rat GAD65 (P = 0.0005). The preference for human GAD65
increased with increasing age at onset (P = 0.0002). This differentiation w
as not observed in 88 GAD65Ab-positive control subjects. Our data indicate
that recognition of epitopes by GAD65Ab in type 1 diabetes is different fro
m that in nontype 1 diabetes, GAD65Ab-positive individuals.