Sensitized recipients exhibit accelerated but not hyperacute rejection of vascularized composite tissue allografts.

Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202-1760, USA.
Transplantation (Impact Factor: 3.78). 08/2011; 92(6):627-33. DOI: 10.1097/TP.0b013e31822b9264
Source: PubMed

ABSTRACT Currently, the donor-recipient matching process for vascularized composite tissue allotransplantation (VCTA) closely follows the standard practices for solid organ transplantation. Sensitization is considered a contraindication to VCTA. However, the role of sensitization in VCTA rejection is largely unstudied.
Major histocompatibility-mismatched ACI (RT1) donors and Wistar Furth (WF) (RT1) recipients were used to determine whether sensitization would lead to hyperacute rejection in VCTA as in other organs, such as kidneys. WF rats were presensitized to ACI antigens by skin transplantation and received heterotopic osteomyocutaneous VCTA flaps. Kidney transplants served as controls.
Production of anti-donor antibody was detected in WF recipients after rejection of the ACI skin grafts. Sensitized WF rats rejected VCTA grafts from ACI rats significantly faster (P<0.05) than unsensitized recipients, but not hyperacutely. Rejection in the sensitized recipients was not prevented by immunosuppression with FK506 and mycophenolate mofetil. In contrast, kidney allografts from ACI rats were hyperacutely rejected within 30 min by sensitized recipients. To confirm the role of antibody-mediated rejection in the sensitized recipients, serum from presensitized rats was adoptively transferred into naïve WF rats. Hyperacute rejection occurred only in transplanted kidneys but not VCTA. Histologic examination of tissues from acceleratedly rejected VCTA showed dense lymphocytic infiltrates, and no antibody deposition.
VCTA are rejected in an accelerated fashion but not hyperacutely in the presence of allosensitization and preformed anti-donor antibody. The rejection of VCTA in sensitized recipients is mainly cell mediated and differs mechanistically from that for renal transplants.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Facial vascularized composite allotransplantation has ushered in a new era in treating complex facial injuries that cannot be reconstructed using traditional techniques. Multiple teams have reported their experiences in monitoring for allograft rejection using skin and mucosal biopsies. The association of biopsy findings and clinical observations are poorly understood and are continuously being redefined. We review the world’s experience in monitoring skin and mucosal histological findings in facial transplantation, review acute rejection, antibody-mediated rejection, chronic rejection, and describe our institutional experience in the monitoring and management of facial allograft histology.
    09/2014; 1(3). DOI:10.1007/s40472-014-0023-8
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advances in microsurgical techniques and immunomodulatory protocols have contributed to the expansion of vascularized composite allotransplantation (VCA) with very encouraging immunological, functional, and cosmetic results. Rejection remains however a major hurdle that portends serious threats to recipients. Rejection features in VCA have been described in a number of studies, and an international consensus on the classification of rejection was established. Unfortunately, current available diagnostic methods carry many shortcomings that, in certain cases, pose a great diagnostic challenge to physicians especially in borderline rejection cases. In this review, we revisit the features of acute skin rejection in hand and face transplantation at the clinical, cellular, and molecular levels. The multiple challenges in diagnosing rejection and in defining chronic and antibody-mediated rejection in VCA are then presented, and we finish by analyzing current research directions and novel concepts aiming at improving available diagnostic measures.
    Frontiers in Immunology 11/2013; 4:406. DOI:10.3389/fimmu.2013.00406
  • [Show abstract] [Hide abstract]
    ABSTRACT: Refinements in microsurgical techniques coupled with advances in immunosuppressive and immunomodulatory protocols have enabled broader clinical application of vascularized composite allotransplantation (VCA) with encouraging immunological, functional, and esthetic results. However, skin rejection remains a significant obstacle and a serious complication for VCA recipients. Clinical and histopathological features of rejection in VCA have been described in a number of studies, which led to the development of an international consensus on the classification guidelines of rejection in the context of VCA. Nevertheless, currently available diagnostic modalities still have several limitations and shortcomings that can pose a significant diagnostic challenge, particularly when signs of rejection are found to be equivocal. In this review, we provide a critical analysis of these advances and challenges in diagnosing skin rejection. Specifically, we highlight the gaps in understanding of rejection mechanisms, the shortfalls in correlating cellular, molecular, and clinicopathologic markers with rejection grades, deficiencies in defining chronic rejection, and antibody-mediated rejection after VCA, as well as providing an outlook on novel concepts, such as the utilization of advanced computational analyses and cross-disciplinary diagnostic approaches.
    Clinical Transplantation 01/2014; 28(3). DOI:10.1111/ctr.12316 · 1.49 Impact Factor