LACK OF AUTOIMMUNE SEROLOGICAL REACTIONS IN RODENT MODELS OF INSULIN-DEPENDENT DIABETES-MELLITUS

Spontaneous insulitis with insulin-dependent diabetes mellitus (IDDM) in rodent models, the BB rat and NOD mouse, has clarified the pathogen esis of and guided decisions on interventional therapy for human IDDM. However, the occurrence in such models of a standard marker of human IDDM, autoantibodies to beta islet cell constituents, has been controv ersial. Hence we assessed diabetes-prone rodents for the frequencies o f raised levels of autoantibodies to glutamic acid decarboxylase GAD ( anti-GAD), insulin and heat shock protein 65 (HSP-65) in relation to l evels in non-diabetes-prone animals and levels in human diabetic sera. Assays were performed sequentially at various ages of life. The immun oassays used for anti-GAD and anti-insulin were those validated for se nsitivity and specificity for detection of the corresponding autoantib odies in human IDDM sera at international workshops. Positive controls included human IDDM sera with reactivity with GAD or insulin and, for mouse anti-GAD, the highly reactive monoclonal antibody, GAD-6. The r esults were that levels of autoantibodies in diabetes-prone BB rats or NOD mice to the 'IDDM-relevant' autoantigens in our panel did not exc eed levels in control rats or mice, and were much lower than levels in humans with IDDM. We conclude that the BE rat and NOD mouse represent a model, but not a facsimile, of human IDDM and that therapeutic succ esses in such models should be interpreted with caution in relation to interventional therapy for human IDDM. (C) 1996 Academic Press Limite d