Pancreatic Allografts: Identification of Useful Biomarkers of Rejection and Beyond

Abstract

Since organ transplantation became routine more than threedecades ago, there has been a need to obtain useful infor-mation regarding graft health, with assessment of the pre-sence of progressive immune-mediated graft rejection ofparticular importance for planning intervention. Althoughthe recommended method is to obtain sequential biopsiesfrom the graft itself, this procedure is invasive and risky,particularly if more than one sample is needed. Therefore,identification of less invasive markers, ideally measureablein the blood of transplant recipients, has been activelyinvestigated. Because of the large number of losses ofpancreatic grafts, it is particularly important to discoversurrogate markers of immune rejection.In this issue of Digestive Diseases and Sciences, Donget al. [1] describe a porcine model of pancreaticoduodenaltransplantation with or without immunosuppression thatwas used to evaluate the effectiveness of three potentialperipheral blood biomarkers of acute rejection for up toseven days post-transplant. The authors selected intercel-lular adhesion molecule (ICAM)-1, Fas cell surface deathreceptor (Fas), and its ligand FasL, all reported previouslyto be involved in the acute rejection response after solidorgan transplantation in humans and in animal models.ICAM-1 is an adhesion molecule involved in firmendothelial adhesion and trans-endothelial migration ofleukocytes, including T cells, monocytes, and neutro-phils, at sites of immune response and immunologicalsynapse formation (reviewed elsewhere [7]). ICAM-1 isconstitutively expressed on the surface of human endo-thelial cells and its expression is increased in the presenceof pro-inflammatory cytokines including tumor necrosisfactor (TNF)-a, interferon (IFN)-c and interleukin (IL)-1b.The most important ligand for ICAM-1 is the b-2 integrinlymphocyte function-associated (LFA)-1 (aLb2); it isexpressed on all types of leukocyte but requires a Ca