Widespread Amyloid Deposition in Transplanted Human Pancreatic Islets

Abstract

To the Editor: We report on a patient with type 1 diabetes mellitus, diagnosed at 16 years of age, in whom widespread amyloid deposits developed many years later in transplanted human islets.The islets were administered through three intraportal infusions: two infusions were administered 4 months apart when the patient was 50 years of age, and one infusion was administered when he was 54 years of age.Before the first implantation, the treatment of the patient, who had a functioning renal transplant, was switched to the Edmonton immunosuppression protocol (i.e., daclizumab, tacrolimus, and sirolimus).After the second islet transplantation, the patient became insulin-independent.The maximum meal-stimulated plasma C-peptide concentration was 1.33 nmol per liter, and the level of glycated hemoglobin was 7.0%.At the age of 51 years, his meal-stimulated C-peptide concentration was 0.95 nmol per liter, and he required a low dose of insulin.Because of slowly deteriorating islet function, he received a third islet infusion 6 months before his death.He died from a myocardial infarction nearly 5 years after the first islet infusion.One month before he died, his fasting serum C-peptide concentration was 0.34 nmol per liter (reference range, 0.3 to 1.3 nmol per liter), his meal-stimulated serum C-peptide concentration was 0.82 nmol per liter, and his glycated hemoglobin level was 6.7%.A total of 89 islets containing insulin-positive cells as well as abundant glucagon-positive cells were observed in 53 different blocks of liver tissue obtained from the patient.Amyloid deposits were identified in 38 islets (43%) (Fig. 1A and 1B).The amount of amyloid varied, but five islets had pronounced amyloid deposits.Most deposits were extracellular (Fig. 1C, 1D, and 1E).Immunoelectron microscopy showed bundles of amyloid fibrils that were positive for antibodies against islet amyloid polypeptide, also within beta cells (Fig. 1F).Pancreatic specimens and specimens of isolated islets from all donors were available, and 2 of about 100 islets obtained from one donor Uppsala University SE-751-85 Uppsala, Sweden per.westermark@genpat.uu.