Insulin autoantibodies in mouse models of insulin-dependent diabetes

To clarify the significance of insulin autoantibodies (IAA) in insulin-dependent diabetes mellitus, we measured the IAA longitudinally in non-obese diabetic (NOD) mice, and in high-dose streptozotocin-induced diabetes (high-SZ) and EMC virus-induced diabetes (EMC) in mice, and compared the data with the occurrence of insulitis. The IAA were detected by the polyethylene glycol (PEG) method using 125I-(Tyr A14) human insulin. The IAA were found in 38% of NOD mice and correlated with the occurrence of insulitis. The prevalence of IAA was 0% before the appearance of insulitis 80% at 12-14 weeks of age and 30% after 20 weeks of age in female NOD mice. In male NOD mice, IAA were found in 45% at 12-14 weeks of age and 20% after 20 weeks. In high-SZ mice, IAA were detected in several mice while insulitis was not present. In EMC-virus induced diabetic mice, IAA and lymphocytic infiltration into the islets were detected 4-14 days after EMC virus infection. These results suggest that (a) IAA are markers for islet autoimmunity in NOD mice, (b) the presence of IAA does not always reflect insulitis, (c) the presence of IAA is not sufficient for the development of overt diabetes and (d) the appearance of IAA may reflect a difference of the immune response genotype.