Antibodies to ICA512/IA-2 in Rodent Models of IDDM

• Published in: Journal of autoimmunity 1998-06, Vol.11 (3), p.265-272
• Main Authors: Myers, M.A, Laks, M.R, Feeney, S.J, Mandel, T.E, Koulmanda, M, Bone, A, Barley, J, Rowley, M.J, Mackay, I.R
• Format: Article
• Language: English
• Subjects: Animals; autoantibodies; Autoantibodies - blood; Autoantigens - immunology; BB rats; Biological and medical sciences; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epitope Mapping; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; IA-2; ICA512; IDDM; Immunity, Innate; Medical sciences; Membrane Proteins - immunology; Mice; Mice, Inbred NOD; Mice, Inbred Strains; NOD mice; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - immunology; Rats; Rats, Inbred BB; Rats, Wistar; Receptor-Like Protein Tyrosine Phosphatases, Class 8
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1998.0192

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 BB rat develop spontaneous diabetes as a consequence of T-cell mediated autoimmune destruction of islet β-cells, but the occurrence of autoantibodies is contro-versial. We tested sera from NOD mice and BB-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 BB rats, low levels of anti-ICA512 were present in 11/20 (55%) of non-diabetic-diabetes prone (DP) BB rats, 0/4 (0%) of diabetic DP BB rats, and 1/6 (17%) of diabetes-resistant BB 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 BB 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.