ANTIBODIES TO ICA512 IA-2 IN RODENT MODELS OF IDDM/

Antibodies to ICA512/IA-2 are a well established marker of human IDDM and can be detected prior to and soon after the onset of insulin depen dency. The non-obese diabetic (NOD) mouse and the diabetes-prone BE ra t develop spontaneous diabetes as a consequence of T-cell mediated aut oimmune destruction of islet beta-cells, but the occurrence of autoant ibodies is controversial. We tested sera from NOD mice and BE-rats for anti-ICA512 by a radioimmunoprecipitation assay (RIP). In sequential serum samples from 20 NOD mice, of which 15 developed diabetes, low le vels of anti-ICA512 were demonstrable. Anti-ICA512 appeared close to t he onset of hyperglycaemia and was usually transient. Non-diabetic NOD mice also produced anti-ICA512, but at a later age and at lower level s than the diabetic NOD mice. In a cross-sectional analysis of sera fr om BE rats, low levels of anti-ICA512 were present in 11/20 (55%) of n on-diabetic-diabetes prone (DP) BE rats, 0/4 (0%) of diabetic DP BE ra ts, and 1/6 (17%) of diabetes-resistant BE rats. Anti-ICA512 was not d etected in rats of other strains, including three Sprague-Dawley rats with streptozotocin-induced diabetes. In both NOD mice and BE rats the anti-ICA512 reactivity was directed to the cytoplasmic domain of the protein. The transient appearance of anti-ICA512 close to the onset of diabetes in NOD mice and the loss of these antibodies after diabetes onset is consistent with the occurrence of anti-ICA512 in human IDDM. Thus in both human IDDM and rodent models, anti-ICA512 is a marker of the impending onset of diabetes and disappears after diabetes onset. ( C) 1998 Academic Press.