Search Tolerance Signature in Vascularised Composite Allograft

Composite tissue allotransplants (CTA) involve transplantation of various tissues including vessels, nerves, skin, bones, and immune cells and entail a significant antigenic load. The large majority of recipients have been maintained on immunosuppression therapy similar to that used in solid organ transplantation that is associated with the complications usually reported in solid organ transplantation. The question whether risks associated with indefinite immunosuppressive are justified for a non-lifesaving procedure still remains unanswered. At present no CTA recipient proved to be spontaneously tolerant with any immunosuppressive protocol; indeed, until now all recipients who discontinued the immunosuppressive therapy rejected their graft. On the other hand CTA recipients showed a low incidence of chronic rejection despite the high incidence of acute rejection episodes. For all these reasons it should be of great interest to minimize the immunosuppression in CTA patients knowing their immunologic "risk". The main outcome of this study is to search for the signature of tolerance in recipients of hand or face allotransplantation testing biomarkers previously identified in operational tolerant kidney transplant recipients. These markers have been developed studying tolerant kidney recipients and they were already tested in five bilateral hand transplantations and one face transplantation. The present study will include hand and face allograft recipients transplanted at least one year in several European institutions (Innsbruck, Lyon, Monza, Valencia): 11 bilateral hand transplantations, 4 single hand transplantations and 3 face transplantations. All the patients will undergo B cell phenotyping, TCR repertoire, molecular signature from operational tolerance and a skin biopsy with immunohistochemical staining of the specimens in order to show signs of acute or chronic rejection. The results could provide a valid tool to detect operationally tolerant recipients as well as recipients prone to develop chronic rejection.