Histologic studies of islets of Langerhans in transplanted pancreata from marginal donors in Japan.

The serious shortage of brain-dead donors leads to the use of pancreata from marginal donors, including cardiac death in Japan. We studied the islet histology of pancreas graft biopsies to investigate the adequacy of using pancreata from marginal donors. Pancreas allograft biopsy was performed originally to diagnose acute rejection (Drachenberg grade I-III) at a mean of 6 months after transplantation. The percentage of beta cells showing oxidative DNA changes, replication, and apoptosis was investigated in 7 recipients of simultaneous pancreas-kidney transplantations with good graft function from marginal donors. Their causes of death were cerebrovascular with donor ages >44 years (n = 3), cardiac (n = 2), and cerebrovascular (n = 2). The percentage of beta cells per islet in the transplanted pancreas (71.9 +/- 3.3%) did not correlate with glycemic control or insulin secretion, but did correlated inversely with donor age (r = -0.81; P < .05). Oxidative DNA changes as revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present in islet cells as well as in the exocrine cells of the transplanted pancreas. The percentage of 8-OHdG-positive cells per pancreas (71.8 +/- 4.5%) did not correlate with glycemic levels, insulin secretion, donor age, or ischemic time. There were no Ki67-positive replicating cells or terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive apoptotic islet cells. Transplanted pancreata from marginal donors showed preserved beta cells and function despite diffuse oxidative changes.

A case of recurrent type 1 diabetes mellitus with insulitis of transplanted pancreas in simultaneous pancreas-kidney transplantation from cardiac death donor.

AIMS/HYPOTHESIS: A 41-year-old woman undergoing simultaneous pancreas-kidney transplantation from an HLA-mismatched cardiac death donor abruptly developed overt hyperglycaemia under standard immunosuppressive therapy at 48 months after transplantation. Unexpectedly, we found insulitis in the transplanted pancreas and characterised the insulitis. METHODS: Pancreas graft biopsies were performed 3 years before and after the development of hyperglycaemia and the specimens were examined histologically. RESULTS: Insulitis was absent in the first biopsy, although oxidative DNA changes revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present both in islet cells and exocrine cells. No Ki67-positive proliferating cells were seen in the islets. Anti-glutamic acid decarboxylase antibody was undetectable 6 months earlier but increased to 6.3 U/l at the development of hyperglycaemia. The level of anti-insulinoma-associated protein 2 antibody was 18.5 U/l. Insulin secretion was severely suppressed and insulin therapy was resumed. In the second biopsy, although acute allograft rejection was minimal, insulin-positive beta cells were markedly reduced, and glucagon-positive alpha cells predominated. CD3-positive T lymphocytes, CD8-positive cytotoxic T lymphocytes and CD68-positive macrophages infiltrated around and into islets. The infiltrating cells expressed Fas ligand as well as granzyme B. More than 80% of islets were affected by insulitis. 8-OHdG-positive cells were also present in islets and exocrine tissue. The percentage of Ki67-positive cells in total islet cells was 1.5%. There were no TUNEL-positive apoptotic cells in the islet cells. CONCLUSIONS/INTERPRETATION: The histological features of insulitis in transplanted pancreas were consistent with common type 1 diabetes mellitus, but the clinical course of the recurrence appeared to be more rapid.