Clinicopathologic Monitoring of the Skin and Oral Mucosa of the First Human Face Allograft: Report on the First Eight Months

Kanitakis, Jean; Badet, Lionel; Petruzzo, Palmina; Béziat, Julien; Morélon, Emmanuel; Lefrançois, N; Françès, Camille; Claudy, A; Martín, Xavier; Lengelé, Benoît; Testelin, Sylvie; Devauchelle, Bernard; Dubernard, Jean Michel

doi:10.1097/01.tp.0000248780.55263.33

Cited by 108 publications

(85 citation statements)

References 11 publications

(12 reference statements)

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“…21 However, clinical assessment, histopathological diagnosis, and immunological mechanisms of facial composite allograft rejection remain incompletely studied, albeit being critical to further refinement of this new treatment option. Although a number of important studies have begun to address the issue of biomarkers and related immunopathology in vascular composite allotransplantation [22][23][24][25][26][27][28][29] (particularly in hand transplantation), our study represents a detailed and sequential histopathologic and immunophenotypic assessment of full facial transplant rejection. Facial allografts represent a unique setting where rejection can be evaluated for cutaneous biomarker expression in multiple and sequential biopsies not required in routine skin allograft transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Resident T cells within tracheal allografts have been shown to be radiation sensitive, 46 raising the possibility that pretransplant irradiation or other means of purging donor T cells from grafts might influence the clinical course of rejection post-transplant. Major strides have already been accomplished in understanding vascular composite allotransplantation rejection and biology, [22][23][24][25][26][27][28][29] and the Banff system is clearly useful in assessing allograft rejection. However, our findings underscore the critical role for further refinements in histopathology and biomarker application to the accurate diagnosis, therapeutic monitoring, and mechanistic understanding of vascular composite tissue transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury

et al. 2014

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This series of 113 sequential biopsies of full facial transplants provides findings of potential translational significance as well as biological insights that could prompt reexamination of conventional paradigms of effector pathways in skin allograft rejection. Serial biopsies before, during, and after rejection episodes were evaluated for clinicopathological assessment that in selected cases included specific biomarkers for donorversus-recipient T cells. Histologic evidence of rejection included lymphocyte-associated injury to epidermal rete ridges, follicular infundibula, and dermal microvessels. Surprisingly, during active rejection, immune cells spatially associated with target cell injury consisted abundantly or predominantly of lymphocytes of donor origin with an immunophenotype typical of the resident memory T-cell subset. Current dogma assumes that skin allograft rejection is mediated by recipient T cells that attack epidermal targets, and the association of donor T cells with sites of target cell injury raises questions regarding the potential complexity of immune cell interactions in the rejection process. A more histopathologically refined and immune-based biomarker approach to assessment of rejection of facial transplants is now indicated. Modern Pathology (2014) 27, 788-799; doi:10.1038/modpathol.2013.249; published online 17 January 2014Keywords: donor T cell; facial transplant; graft-versus-host disease; skin allograft; T resident memory cells; vascularized composite allotransplantation Recent reports emphasizing the critical therapeutic importance of accurate diagnosis of transplant rejection 1 have stressed the imminent need for more precise clinicopathologic criteria and complementary application of relevant biomarkers. 2 The first systematic studies of any form of human allograft rejection were reported by Gibson and Medawar 3 in their classic description of skin rejection involving wartime aviators. 4 Early clues regarding the immunologic basis of skin graft rejection came from studies by Dvorak et al 5 and Bhan et al 6 that implicated both CD4 þ and CD8 þ T cells. These T-cell populations were presumed to be of recipient origin and considered to be primary effectors of epidermal and dermal microvascular target cell injury. With the recent advent of fullfacial transplantation, 7 detailed and sequential histopathologic surveillance for rejection in a manner seldom feasible for conventional skin allografts has become a necessity. However, existing schemas 8 for histologic recognition and grading of rejection in vascular composite allotransplantation are based primarily on allografts that may express relevant structural and immunological differences from facial tissues, eg, extremities (hand) and

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury

et al. 2014

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“…The skin is the most important and largest component of FAT, and it is well known that the skin (and the mucosa) has a high immunogenicity, so it is inevitable that rejection episodes are triggered at different times: [33,69] in the early period (hyper-acute rejection), within days or months after transplantation (acute rejection) or chronic rejection. [55,70] Hyper-acute graft rejection has not been reported so far.…”

Section: Inmunologymentioning

confidence: 99%

Current role in facial allograft transplantation: what have we learned?

Infante-Cossio¹,

Barrera-Pulido²,

Gómez-Cía³

et al. 2016

PAR

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Face transplant (FT) has evolved enormously in the last 10 years since the successful completion of the first facial transplant. This procedure has become a new reconstructive option for complex facial deformities to restore the anatomy of patients with severely disfigured faces. The authors review the literature and discuss the main surgical, immunological, and ethical aspects as well as the results described in patients undergoing FT. To date there have been more than thirty FT worldwide. The main indication was post-traumatic deformity. In all cases a standard immunosuppression was performed with three drugs, although acute rejection episodes were observed, that could be controlled with conventional immunosuppressive regimen. Overall, functional and aesthetic results have been excellent at short-term and high satisfaction rate exceeded initial expectations, although long-term data are still scarce. Major complications were opportunistic infections. Five deaths that occurred have reopened the ethical debate about the potential complications and concerns of providing informed consent to recipients. Continuous progresses in microsurgical techniques and preoperative planning have promoted the evolution from partial to full FT. All these are on the basis of accurate and careful selection of wellmotivated candidates. The next challenge will be getting new immunosuppressive treatment strategies. Although clinical experience has demonstrated the FT viability, it is still considered an experimental procedure in which we have much to learn to define its true role in the current reconstructive surgery and resolve major technical, medical and ethical problems involved.

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“…Maintenance therapies have been adjusted by dose reduction to minimize adverse effects while preventing graft rejection. In some recipients, topical ointment of calcineurin inhibitors and steroids was applied to avoid or treat skin rejection [8,9].…”

Section: Immunosuppression In Face Transplantationmentioning

confidence: 99%

Minimization of Immunosuppression and Tolerance Induction in Reconstructive Transplantation

et al. 2012

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Vascularized composite allotransplantation (VCA) is an innovative reconstructive modality for patients sustaining complex injuries not amenable to conventional treatment. Advances in immunosuppression have made VCA a clinical reality and a valid reconstructive option for such patients. The requirement, however, for multi-drug high-dose immunosuppressive regimens with their numerous side effects has hindered widespread clinical application of VCA. There is thus a need for novel immunologic modalities to minimize or even obviate the need for immunosuppression (tolerance induction) while still preserving the allograft and preventing rejection. Recent advances in targeted immunotherapy and cell-based protocols were able to achieve tolerance in selected cases of solid organ transplantation. This paved the way for innovative immunomodulatory protocols now also applied to VCA that aim for minimal immunosuppression or for induction of donor-specific tolerance. These concepts and novel protocols will be discussed in this review.

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Clinicopathologic Monitoring of the Skin and Oral Mucosa of the First Human Face Allograft: Report on the First Eight Months

Cited by 108 publications

References 11 publications

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury

Current role in facial allograft transplantation: what have we learned?

Minimization of Immunosuppression and Tolerance Induction in Reconstructive Transplantation

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