Plasma citrulline levels and acute cellular rejection early after small bowel transplantation in pigs

Small bowel transplantations (SBT) are increasingly performed to treat patients with irreversible intestinal failure or short-bowel syndrome. Histologic evaluation of small bowel allograft biopsies is important for the diagnosis of acute cellular rejection (ACR). A reliable serological marker of ACR after SBT is still unknown. Recently, citrulline was identified as a potential biomarker of reduced enterocyte mass. The aim of our study was to analyze rejection and plasma citrulline levels early after SBT in pigs. 24 pigs were used and divided into four groups. Group A, autologous SBT (n = 3) as a control group; Group B, allogeneic SBT with tacrolimus monotherapy (n = 7); Group C, allogeneic SBT immunosuppressed with tacrolimus and sirolimus (n = 8); and Group D, without immunosuppresion (n = 6). The observation period was 30 days. Mucosal biopsies were obtained on Days 0, 3, 5, 7, 10, 14, 20, 28 and simultaneously plasma citrulline levels were measured. ACR was classified according to standardized grading schema on a scale of indeterminate, mild, moderate, and severe. There were no significant differences in citrulline plasma levels between cases with mild ACR and indeterminate for ACR. A significant decline in plasma citrulline levels occurred in cases of moderate and severe rejection. Plasma citrulline levels constituted a marker of more advanced injury of small bowel epithelium.