Molecular Signature of Acute Rejection in Clinical Face Transplants
Technical Report,15 Jul 2017,14 Jul 2019
Brigham and Womens Hospital Boston United States
Pagination or Media Count:
Rejection is the primary barrier to broader implementation of vascularized composite allografts. Diagnosis of rejection currently relies on histological assessment of skin biopsies according to the 2007 Banff criteria. The purpose of this study was to systemically interrogate the molecular mechanism underlying clinical facial allograft rejection. We also compared it to solid organ transplant rejection and non-transplant inflammatory skin diseases. Grade 1 rejection did not differ significantly from non-rejection, suggesting that it does not represent a pathologic state and that watchful waiting is warranted. Grade 2 rejection had evidence of Th1 activation and upregulation of T cell co-stimulatory as well as co-inhibitory pathways. IFNy-driven cytotoxicity, tissue injury and upregulation of immunoregulatory pathways were present in Grade 3 rejection. Rejection of VCA and solid organ transplants had both distinct and common features. VCA rejection was uniquely associated with upregulation of immunoregulatory genes and induction of lipid antigen-presenting CD1 proteins. These genes were unique to rejection and not upregulated in non-transplanted individuals with inflammatory skin diseases. Our findings suggest that the distinct features of VCA rejection reflect the unique immunobiology of skin and that enhancing cutaneous immunoregulatory networks may be a useful strategy in combating rejection.
- Medicine and Medical Research