Rejection affects greater than 80% of face transplants, yet no diagnostic criteria for antibody-mediated rejection (AMR) following face transplantation have been established. Given that different treatment strategies are required to address AMR and T cell–mediated rejection (TCMR), there is a critical need to delineate the features that can differentiate these two alloimmune responses. Here, we report the longitudinal immunological examination of what we believe to be the first and only highly sensitized recipient of a crossmatch-positive face transplant up to 4 years following transplantation. We conducted gene expression profiling on allograft biopsies collected during suspected AMR and TCMR episodes as well as during 5 nonrejection time points. Our data suggest that there are distinctive molecular features in AMR, characterized by overexpression of endothelial-associated genes, including ICAM1, VCAM1, and SELE. Although our findings are limited to a single patient, these findings highlight the potential importance of developing and implementing molecular markers to differentiate AMR from TCMR to guide clinical management. Furthermore, our case illustrates that molecular assessment of allograft biopsies offers the potential for new insights into the mechanisms underlying rejection. Finally, our medium-term outcomes demonstrate that face transplantation in a highly sensitized patient with a positive preoperative crossmatch is feasible and manageable.
Thet Su Win, Naoka Murakami, Thiago J. Borges, Anil Chandraker, George Murphy, Christine Lian, Victor Barrera, Shannan Ho Sui, David Schoenfeld, Jessica Teague, Ericka Bueno, Stefan G. Tullius, Bohdan Pomahac, Rachael A. Clark, Leonardo V. Riella
Dynamics of circulating B cells and T follicular helper cells following facial transplantation.
Contour plots of naive (CD19+CD27–IgD+), nonclass-switched memory (non-sw-Ig: CD19+CD27+IgD+), and class-switched memory (sw-Ig: CD19+CD27+IgD–) B cells (top) and CD4+PD1+CXCR5+ cells (T follicular helper cells [cTfh]) (bottom) before transplant and at 1 week (suspected AMR), 22 months (nonrejection time point), and 24 months after transplant (TCMR3). Relative percentages of both non-sw-Ig and sw-Ig B cells and Tfh cells increased at 1 week after transplant, corresponding to the increase in DSAs and the suspected AMR episode.