Disappeared Islet Graft after Intraportal Transplantation in the Recipient Suffered from Recurrent Sepsis

Background: Pancreatic islet transplantation is an emerging treatment option for type 1 diabetes mellitus, however, insulin independence is gradually lost over time in most cases. The lack of methods to monitor β-cell mass render the intrahepatic grafted islets a “black box”. A detailed pathological finding of intraportally grafted islets in autopsy specimen would make a significant contribution to understand islet engraftment. We report a finding of autopsy from a patient who received three consecutive islet transplants. She suffered from recurrent sepsis after transplant and ultimately lost C-peptide secretion. Clinical case: A 41 years old female suddenly died of an acute pulmonary thromboembolism 4 years after third islet transplant. The patient underwent three islet transplants by infusion of islets into the portal vein with daclizumab induction and sirolimus and tacrolimus maintenance (the Edmonton protocol). All transplants were isolated from donors after cardiac death, given 14 and 21 months after the first transplant, respectively. She had good glycemic control and low insulin requirement (0.2-0.3U/kg/day) after transplant, but had not achieved insulin independence. Immunosuppressive drugs were reduced and discontinued due to recurrent sepsis by acute cellulitis or catheterassociated infection. Finally, fasting serum C-peptide concentrations were quite low (< 0.3 ng/ml) 3 years after final transplant. Result: A complete autopsy was performed. No transplanted islets were identified in the portal vein area. There were no tissues or cells stained for insulin and chromogranin in the liver, and no amyloid fibrils were identified. Multiple hepatic microabscesses were observed with CD15 positive neutrophil infiltration around zone II (transition zone) and zone III (centrilobular), suggesting possible involvement of recurrent hematogenous infection. The entire pancreas was submitted for histological review and few islets without staining insulin were identified. Conclusion: This report shows that the pathological appearance of the “end-stage islet graft” infused to the portal vein. No evidence was found to support an immunological basis or a non-immunological basis for the loss of intrahepatic islets, and the causal linkage between hepatic microabscesses and graft loss cannot be confirmed. Possible reasons for islet graft loss should be discussed to establish safer and more attractive islet transplantation.

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