Chronic rejection in vascularized composite allografts.

Abstract

To convey key issues surrounding chronic rejection in vascularized composite tissue allotransplantation (VCA), and to highlight pathologic features consistent with VCA chronic rejection. Features consistent with chronic rejection have been reported in three VCA animal models, and have been observed in a paucity of human knee and hand transplants. These features include transplant vasculopathy with intimal hyperplasia, tertiary lymphoid follicles, graft fibrosis, and graft edema. Transplant vasculopathy has been the most consistent finding across cases, and has resulted in graft dysfunction and loss. Antibody-mediated rejection has not been conclusively reported in animal models or human subjects, although some cases have demonstrated donor-specific antibody in conjunction with C4d deposition. Multiple immunologic and non-immunologic mechanisms of VCA chronic rejection have been proposed. As in solid organ transplantation, chronic rejection in VCA remains ill-defined. Transplant vasculopathy appears to be a key feature of chronic VCA rejection, whereas tertiary lymphoid follicles, graft fibrosis, and graft edema appear to be less-specific findings. Intimal hyperplasia can be detected with advanced imaging modalities.