Immunological Challenges in Vascularised Composite

Authors: Emmanuel Morelon Jean Kanitakis Palmina Petruzzo Lionel Badet Olivier Thaunat

Publish Date: 2015/07/02

Volume: 2, Issue: 3, Pages: 276-283

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Abstract

Vascularised composite allotransplantation VCA is a new field in transplantation aiming to improve disabled patients’ quality of life Two tissues appear to play an important role in the immune response the skin which is highly immunogenic and the main target of Tlymphocytemediated acute rejection and the vessels which are targeted by the humoral arm of recipient’s immune response which lead to chronic rejection as in solid organ transplantation In preclinical models transplantation of bone marrow is associated with mixed chimerism inducing and maintaining tolerance to allogeneic VCA However this is not the case clinically Immunosuppression used in VCA patients is similar to that in solid organ transplantation with similar side effects and complications However as a lifeenhancing transplant the careful selection of recipients and a close followup cannot be overemphasisedComposite tissue allotransplantation CTA or vascularised composite allotransplantation VCA is defined as the simultaneous transplantation of several tissues including skin muscles tendons nerves vessels bone marrow cartilage and bones which are transplanted as a single functional unit from a deceased donor to a recipient These allografts have recently become a clinical reality following the advances in microsurgery and immunosuppressive therapy Hand and facial allografts are the most common examples of VCA More than 60 patients have undergone upper limb—namely the hand forearm and arm—allotransplantation and 35 have received a face transplant 1 IRHCTT wwwhandregistrycom Other VCAs such as larynx femur knee abdominal wall lower limbs and uterus have been performed This article will focus on upper extremity and facial allotransplantations the most commonly performed and with the longest followupThe functional and aesthetic outcomes after limb transplantation allow amputees to regain manual dexterity to perform most daily activities Functional recovery is based on sensitivity and motion recovery In our experience six cases of bilateral hand allotransplantation all recipients experienced adequate sensorimotor recovery protective and tactile sensitivity and partial recovery of intrinsic muscles and became able to perform the majority of activities of daily life allowing for a normal social life 2 3• During the first postgraft year all of them showed protective sensibility and partial recovery of tactile sensitivity while discriminative sensitivity was absent After 2 years tactile sensibility improved and partial recovery of discriminative sensitivity was achieved Motion recovery started between 3 and 6 months Extrinsic muscle function allowed the patients to grasp large objects while intrinsic muscle function started later between 9 and 12 months and increased during the first five posttransplant years Muscular power was weak in all patients ranging from a grip strength of 26 to 16 kg and from a pinch grip 05 kg to a pinch grip 2 kg All recipients considered their quality of life significantly improved after transplantation The recovery of sensitivity and motion was longer in the recipients with a more proximal level of amputation although the final functional recovery was not differentComplete functional restoration is conditioned by nerve regeneration which has been shown to occur by immunohistochemical studies of the skin electromyography and sensitive recovery tests Functional magnetic resonance imaging fMRI and transcranial magnetic stimulation 4•• 5 showed that hand transplantation induces a global remodelling of the limb cortical map reversing the functional reorganisation induced by the amputationThe overall results so far highlight the importance of patients’ compliance to immunosuppression and rehabilitation programme which must be evaluated in detail prior to transplantation As a lifeenhancing transplant it is important to evaluate the real possible functional recovery the patients’ expectations and motivations and their understanding of the undertakingFacial transplantation must be reserved to disfigurements which cannot be corrected satisfactorily by conventional reconstructive surgery Some complex deficiencies need numerous procedures to be reconstructed with nevertheless uncertain outcomes moreover some disfigurements include muscles such as the orbicular ones which cannot be repaired by surgical reconstruction techniques Face transplant recipients have shown aesthetic and functional recovery after transplantation Indeed in our experience they regained the ability to speak eat and swallow—functions that are often affected by disfigurement Remarkable aesthetic results allow them to resume a social life 6 7 8 9 10 In all cases a return to body integrity considerably improves the patients’ quality of life 11The major limit of VCA development is the need for a lifelong immunosuppression and the associated risks which counterbalances the functional results seen so far Herein we will consider the various aspects and mechanisms involved in VCA rejection processes and the immunosuppression treatment used to prevent them

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