Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients)

Abstract

Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss. Dermal sclerosis and adnexal atrophy are additional features of CR. The pathogenetic immune mechanisms involved (cell-mediated versus humoral) remain incompletely known. The changes of CR can be detected with skin and deep tissue biopsies. Modern in vivo imaging tools can detect vascular narrowing and have the advantage of being noninvasive. However, the diagnosis and treatment of CR remain challenging, as several important questions remain to be answered: a more accurate definition of CR in VCA is needed to establish criteria allowing an accurate and early diagnosis. The pathogenetic mechanisms of CR need to be better understood to allow more efficacious treatment. Favoring/triggering factors of CR need to be better known so that they can be avoided. As in SOT, there is a need for efficient tolerance-inducing protocols that will favor graft acceptance and (ideally) circumvent the necessity of lifelong immunosuppression.

Long-term Tolerance Toward Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using Bone Marrow or Mobilized Stem Cells

“…10,11 Efforts to limit the use of immunosuppression or to transplant donor marrow without preconditioning to prevent these complications has led to acute rejection and even loss of the allograft. 12–15 …”

Chronic rejection of human face allografts

“…in clinical morphology and histology of facial allografts distinct from those of NR and AR occurred in 3 of 7 facial transplant recipients. Indeed, prompt diagnosis and treatment of AR episodes are considered as a potential explanation for the low incidence of CR episodes across all VCA centers,3 although the time-course required for the eventual development of CR remains unknown.The first patient previously described in the literature developed T cell-mediated CR of the allograft after a programmed reduction of immunosuppressive therapy due to complications 11. Indeed, prompt diagnosis and treatment of AR episodes are considered as a potential explanation for the low incidence of CR episodes across all VCA centers,3 although the time-course required for the eventual development of CR remains unknown.The first patient previously described in the literature developed T cell-mediated CR of the allograft after a programmed reduction of immunosuppressive therapy due to complications 11.…”

Transplants for non-lethal conditions: a case against hand transplantation in minors

“…These are generally rapidly identified due in part to the high degree of immunological activity skin possesses making the first signs of rejection readily visible 20. While it was initially believed that chronic rejection would not be a significant issue, experience with more patients has demonstrated that, similar to other allografts, low-grade chronic rejection can occur 21. However, there is also no reason to believe that hand transplantation would be substantially different from solid organ transplantation when it comes to chronic rejection and long-term graft survival 5.…”