Antibodies to ICA512/IA-2 in rodent models of IDDM

Myers, MA; Laks, MR; Feeney, SJ; Mandel, TE; Koulmanda, M; Bone, A; Barley, J; Rowley, MJ; Mackay, IR

Author(s): Myers, MA; Laks, MR; Feeney, SJ; Mandel, TE; Koulmanda, M; Bone, A; Barley, J; Rowley, MJ; Mackay, IR;
Details: Publication Year 1998-06,Volume 11,Issue #3,Page 265-272
Journal Title: JOURNAL OF AUTOIMMUNITY
Publication Type: Journal Article
Abstract: 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 dependency. The non-obese diabetic (NOD) mouse and the diabetes-prone BE rat develop spontaneous diabetes as a consequence of T-cell mediated autoimmune destruction of islet beta-cells, but the occurrence of autoantibodies 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 levels of anti-ICA512 were demonstrable. Anti-ICA512 appeared close to the onset of hyperglycaemia and was usually transient. Non-diabetic NOD mice also produced anti-ICA512, but at a later age and at lower levels than the diabetic NOD mice. In a cross-sectional analysis of sera from BE rats, low levels of anti-ICA512 were present in 11/20 (55%) of non-diabetic-diabetes prone (DP) BE rats, 0/4 (0%) of diabetic DP BE rats, and 1/6 (17%) of diabetes-resistant BE rats. Anti-ICA512 was not detected 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.
Publisher: ACADEMIC PRESS LTD
Keywords: GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIGEN-512; DIABETES-MELLITUS; NOD MICE; AUTOANTIBODIES; INSULIN; AUTOANTIGEN; EXPRESSION; DISEASE; MOUSE
Publisher's Version: https://doi.org/10.1006/jaut.1998.0192
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1998-06-01 12:00:00