Autoantibodies to glutamate decarboxylase detected in diabetes-prone BB/OK rats do not distinguish onset of diabetes

Summary

The diabetes Syndrome of the BB rat resembles human Type 1 (insulin-dependent) diabetes including the prevalence of autoantibodies to the 64 kDa Beta-cell autoantigen, which has been identified as glutamate decarboxylase. This study aimed at detecting the prevalence and level of glutamate decarboxylase autoantibodies in 120-day-old diabetic and non-diabetic diabetes-prone BB/OK rats compared to those of sex- and age-matched diabetes-resistant LEW.1A rats. The antibodies were detected using semipurified glutamate decarboxylase from rat brain in two immunoassays, a direct and a sandwich enzyme-linked immunosorbent assay. For the last assay autoantibody-containing immunoglobulins of a serum from a patient with the stiff-man syndrome were used to bind specifically the enzyme as autoantigen in plástic wells. The antibody levels measured as optical density at 490 nm (x ± SD)/prevalence of the diabetic group (120 ± 29 days of age) of BB/OK rats 0.57 ± 0.29 (n = 51)/88% as well as those of the non-diabetic group (121 ± 26 days of age) with 0.51 ± 0.29 (n = 32)/97% was significantly increased (p < 0.01) compared to those of the diabetes-resistant control group 0.15 ± 0.06 (n = 29)/0%. Furthermore in a 209 ± 27-day-old group (n = 21) of non-diabetic but diabetes-prone BB/OK rats the autoantibody levels of 1.21 ± 0.39 vs 0.51 ± 0.26 were further significantly enhanced (p < 0.01). These results were confirmed by a sandwich assay. We conclude that the prevalence of autoantibodies to glutamate decarboxylase is closely associated with the genetic susceptibility to diabetes, but they are not a predictive marker for the onset of diabetes, at least in the BB/OK rats.

Key words

Autoantibodies - ELISA - autoantigen - glutamate decarboxylase - diabetes-prone BB rat