Intercellular Adhesion Molecular-1, Fas, and Fas Ligand as Diagnostic Biomarkers for Acute Allograft Rejection of Pancreaticoduodenal Transplantation in Pigs

Abstract

The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.