Current opinion in organ transplantation
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Curr Opin Organ Transplant · Dec 2014
ReviewAcute rejection in vascularized composite allotransplantation.
Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. ⋯ Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.
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Curr Opin Organ Transplant · Dec 2014
ReviewThe unique immunobiology of the skin: implications for tolerance of vascularized composite allografts.
Vascularized composite allograft (VCA) transplantation restores function and form following major soft tissue and musculoskeletal injury. Lifelong immunosuppression is necessary for graft function and survival but acute skin-targeted rejection episodes remain common. We review recent advances in skin immunobiology, emphasizing findings in clinical and experimental VCAs. We also highlight advances in immunotherapy and tolerance protocols with implications for the prevention of VCA rejection, and ultimately, induction of clinically applicable strategies for VCA tolerance. ⋯ Most VCA transplant centers continue to utilize antibody-mediated induction therapy and triple agent maintenance immunosuppression. Skin remains the primary target of rejection in VCAs, and current multicenter studies hope to elucidate the mechanisms involved. Proposed standardized procedures for skin biopsies, and diligent reporting of clinical data to the international registry, will be important to maximize the strength of these studies.
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Curr Opin Organ Transplant · Dec 2014
ReviewThe potential role for regulatory T-cell therapy in vascularized composite allograft transplantation.
Vascularized composite allograft (VCA) transplantation restores defects to a degree not possible by conventional techniques. However, it is limited by the need for long-term immunosuppression and high rates of acute rejection directed against skin. There is therefore a need for a therapy that may shift the risk-benefit ratio in favour of VCA transplantation. Regulatory T cells (Tregs) are a subset of T cells with potent immunoregulatory properties and the potential to promote immunosuppression-free allograft survival. In this review, we consider the evidence for Treg therapy in VCA transplantation. ⋯ An improvement in outcomes after VCA transplantation has the potential to revolutionize the field. Several effective therapeutic strategies have demonstrated great promise experimentally, and there is now a need to assess their safety and efficacy in a clinical setting.
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Curr Opin Organ Transplant · Dec 2014
ReviewNovel immunosuppressive strategies for composite tissue allografts.
Vascularized composite tissue allografts (CTAs) provide excellent restorative options for patients with limb loss and other deformities. Acute rejection remains common with CTA and immunosuppression is used in an attempt to prevent rejection. This has created ethical debates regarding the use of intensive immunosuppression for a nonlife-saving procedure. This highlights the need for newer immunosuppressive strategies for CTA, which are described in this review. ⋯ Although recent advancements have been made in the immunosuppressive strategies in CTA, the ideal immunosuppression strategy with low toxicity and infection risk but with the ability to prevent acute and chronic rejection is yet to be discovered.