TREATMENT WITH GAD65 OR BSA DOES NOT PROTECT AGAINST DIABETES IN BB RATS

The Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) has been implicated as the initiating islet cell antigen in the pathogenesis of diabetes, primarily based on studies in non-obese diabetic (NOD) nice . To test the role of this islet cell autoantigen in the pathogenesis of spontaneously occurring diabetes in another animal model, purified recombinant human islet GAD65 was injected i.v. at 200 mu g/animal int o 18-day-old diabetes-prone BB rats. For controls, bovine serum albumi n (BSA), which has also been implicated in the pathogenesis of diabete s, or buffer alone was injected into age matched BB rats. At 210 days of age there were no differences in diabetes incidence in the 3 groups , i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA- treated and 65% (11 of 17) in the buffer-treated animals, or in the me dian age at onset of disease, i.e. 79 days (range 65-111), 87 days (ra nge 60-107) and 86 days (range 74-109), respectively. The lack of prot ection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat isle t cells. However, immunohistochemistry of pancreata and immunoblotting analysis of isolated islets showed, that the expression of GAD65 and GAD67 was similar in BE and Lewis rats. In conclusion, these data indi cate that neither GAD65 nor BSA autoimmunity is important for the deve lopment of diabetes in BB rats, in contrast to the situation in NOD mi ce, and further emphasizes that extrapolation from only one animal mod el to autoimmune diabetes in general may not be appropriate.