Aims/hypothesis A 41-year-old woman undergoing simultaneous pancreas-kidney transplantation from an HLAmismatched 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.

The expression of secretory phospholipase A 2 (sPLA 2) is induced by inflammatory stimuli in various cells, and sPLA 2 contribute to produce proinflammatory lipid mediators via hydrolyzing plasma membrane phospholipids into free fatty acid and lysophospholipid. We studied the expression of group IIA sPLA 2 in human islets of transplanted pancreas before and after the recurrence of type 1 diabetes mellitus in a case study. In addition, the effects of exogenous sPLA 2 in isolated rat islets were investigated. Expression of group IIA sPLAs was immunohistochemicaly investigated in the pancreas graft biopsy specimens. Insulin secretion was evaluated by static incubation with different concentrations of snake venom sPLA 2. Intracellular free Ca ( 2) + concentration was measured with Fura 2 and lysophosphatidylcholine (LPC) contents in islets were determined by electrospray ionization-liquid chromatography/mass spectrometry. Group IIA sPLA 2 was not expressed in islets without insulitis before the recurrence, whereas it was diffusely expressed in islets after the recurrence with insulitis. There were cells co-expressing group IIA sPLA 2 and insulin. sPLA 2 dose-dependently induced insulin secretion in isolated rat islets, which was completely prevented by a specific sPLA 2 inhibitor indoxam. The application of sPLA 2 did not affect intracellular free Ca ( 2) + concentration in β cells. On the other hand, LPC contents in islets were significantly increased in sPLA 2-treated islets compared with untreated islets. Incubation with indoxam suppressed the sPLA 2-induced increase of LPC. In conclusion, the present study suggests that group IIA sPLA 2 may be expressed in islets during insulitis in humans. Although sPLA 2 induced insulin secretion in vitro probably via the production of lysophospholipid, the significance of this enzyme expression in insulitis remains elusive.

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