RESUMO
Differential protein glycosylation in the donor and recipient can have profound consequences for transplanted organs, as evident in ABO-incompatible transplantation and xenotransplantation. In this study, we investigated the impact of altered fucosylation on graft acceptance by using donor mice overexpressing human α1,2-fucosyltransferase (HTF). Skin and heart grafts from HTF transgenic mice were rapidly rejected by otherwise completely matched recipients (median survival times 16 and 14 days, respectively). HTF skin transplanted onto mice lacking T and B cells induced an natural killer cell-mediated innate rejection crisis that affected 50-95% of the graft at 10-20 days. However, in the absence of adaptive immunity, the residual graft recovered and survived long-term (>100 days). Experiments using "parked" grafts or MHC class II-deficient recipients suggested that indirect rather than direct antigen presentation plays a role in HTF skin graft rejection, although the putative antigen(s) was not identified. We conclude that altered glycosylation patterns on donor tissue can trigger a powerful rejection response comprising both innate and adaptive components. This has potential implications for allotransplantation, in light of increasing recognition of the variability of the human glycome, and for xenotransplantation, where carbohydrate remodeling has been a lynchpin of donor genetic modification.
Assuntos
Fucosiltransferases/metabolismo , Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , Complexo Principal de Histocompatibilidade/fisiologia , Transplante de Pele/efeitos adversos , Transplante Heterólogo/efeitos adversos , Animais , Apresentação de Antígeno/imunologia , Feminino , Fucosiltransferases/genética , Glicosilação , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Técnicas Imunoenzimáticas , Células Matadoras Naturais/imunologia , Depleção Linfocítica , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Linfócitos T/imunologia , Doadores de Tecidos , Transplante Homólogo , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
A young man with known steroid refractory terminal ileal Crohn's disease developed torrential gastrointestinal bleeding necessitating an emergency ileal resection. Serology was indicative of primary cytomegalovirus (CMV) infection and this was confirmed with histopathology of the resected ileum. We highlight the difficulty in clinical practice of distinguishing between CMV infection and CMV disease as well as the different investigations available to aid in the diagnosis of pathogenic CMV disease.
