Islet autoantibodies as potential markers for disease recurrence in clinical islet transplantation

At present, indications for clinical islet transplantation exist almost exc lusively in type-1 diabetic patients with end-stage renal disease receiving the islets either simultaneously with or after an already established kidn ey graft. This implies, that islet transplantation is performed in type-1 d iabetic patients with long disease duration. The fate of the islet allograf t is determined by a combination of immunological effector mechanisms. Besi de early non-specific inflammation and alloreactivity, chronic autoimmunity may contribute to islet graft failure. The immunologic characterization of the prediabetic state has considerably progressed, whereas, the nature of autoimmunity years and decades after the onset of diabetes is largely unkno wn. Islet autoantibodies as surrogate markers for islet autoimmunity are we ll established in prediabetic periods of type-1 diabetes. In contrast, only few data exists in the setting of long-term type-1 diabetic patients under going islet transplantation. This article reviews the original data from th e Giessen islet transplantation project and the pertinent literature with r espect to islet autoimmunity and disease recurrence. It is demonstrated, th at autoimmunity may persist in an individual with type-1 diabetes for decad es after diabetes onset and that autoimmune responses to transplanted islet s are resistent to the immunosuppressive drugs currently used. It is sugges ted from pilot trials, that type-1 diabetic patients with persistent autoan tibodies and individuals, in whom autoantibodies become detectable after th e transplantation are at higher risk for early islet graft failure potentia lly due to recurrent autoreactivity directed to the islet graft.