Insulin autoantibodies are associated with islet inflammation but not always related to diabetes progression in NOD congenic mice.
Susceptibility to diabetes in humans and nonobese diabetic (NOD) mice is believed to arise from the combined effect of multiple genetic loci, resulting in immune-mediated destruction of the insulin-secreting beta-cells. Insulin autoantibodies (IAAs) are often present in humans for years, and in NOD mice for weeks, before the onset of diabetes. We have evaluated the expression of IAAs in NOD mice and in diabetes-resistant NOD congenic strains to characterize the association of autoantibody expression with insulitis and diabetes. In NOD congenic strains with genes that contribute to protection from insulitis and diabetes (Idd3, Idd5, Idd10, and Idd18), the prevalence of IAAs is reduced relative to NOD mice. In contrast, NOD.B10 Idd9 mice have a high prevalence of IAAs and a high degree of insulitis, despite a nearly complete resistance to diabetes. These data indicate that IAA expression is a phenotype that is associated with insulitis and correlates with overall disease progression in some strains of congenic mice but not in others. It is likely that patients with type 1 diabetes will also show non-major histocompatibility complex genetically determined variation in expression of autoantibodies and progression to diabetes.
Robles
David T
DT
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA.
Eisenbarth
George S
GS
Dailey
Natalie J M
NJ
Peterson
Laurence B
LB
Wicker
Linda S
LS
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D007328:Insulin / Q000276:immunology*; D007330:Insulin Antibodies / Q000097:blood*; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD
D001323:Autoantibodies; D007328:Insulin; D007330:Insulin Antibodies