Regulation of autoimmune diabetes: characteristics of non-islet-antigen specific therapies

Non-islet-antigen specific treatments have been shown to alter the natural history of insulin dependent diabetes in both the non-obese diabetic (NOD) mouse and in recently diagnosed patients. However concerns have been raised regarding the possibility that non-islet-antigen specific therapy may trade cell mediated autoimmunity for antibody dependent autoimmunity. Female NOD mice at approximately 70 days of age were treated with the non-islet-antigen specific agents complete Freund's adjuvant (CFA) and Bacillus Calmette-Guerin (BCG) and assayed for the development of antibody mediated autoimmunity at 300 days of age. Autoantibodies to red cells were not detected in any of the BCG (n = 19) or CFA (n = 15) treated animals, while 2 of 13 age-matched NOD animals had autoantibodies to red cells, shown by a positive direct Coomb's test. Anti-nuclear autoantibodies and complement deposition in the renal glomeruli were not significantly increased in the treated animals as compared to age-matched non-diabetic mice. The relative effectiveness of CFA and BCG treatment was examined in terms of the ability of these agents to preserve insulin containing islets. Complete Freund's adjuvant treatment was found to be more effective in preserving insulin containing islets when compared to BCG treatment. This study demonstrates that it is possible to inhibit the development of autoimmune diabetes without increasing the probability that treated animals will develop antibody dependent autoimmunity.