Longitudinal immunological characterization of the first presensitized recipient of a face transplant
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
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
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Research Article Immunology Transplantation

Longitudinal immunological characterization of the first presensitized recipient of a face transplant

Abstract

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.

Authors

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

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Figure 6

Gene expression profiling of allograft skin biopsies suggests distinctive features in the suspected AMR episode compared with TCMR episodes.

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Gene expression profiling of allograft skin biopsies suggests distinctiv...
(A) Unsupervised principal component analysis performed on 80 genes differentially expressed in a unpaired 2-tailed t test comparing rejection (n = 4) to nonrejection (n = 5) samples (adjusted P ≤ 0.1) suggested a separation of the AMR biopsy from TCMR biopsies along the first principal component. (B) These 80 genes were ranked using the absolute value of their loadings from the first principal component, which was thresholded at 0.1, to identify those contributing most to the observed variability between AMR and TCMR. This yielded 31 genes. The heatmap shows the expression of these 31 genes. Each column represents a facial allograft biopsy, labeled according to whether it was collected during the suspected AMR (red) or TCMR (blue) episodes. The expression of these genes clustered the samples according to the type of rejection. (C) In the volcano plot, the association strength (y axis) is compared with log2 fold change (x axis) in rejection (n = 4) versus nonrejection (n = 5) biopsies. The area shaded in green represents log2 fold change ≥1 and adjusted P ≤ 0.1. (D) Representative images of biopsies collected during the suspected AMR episode and the TCMR episode at 12 months following transplant. AMR was associated with substantially more endothelial adhesion molecule ICAM1 expression in vessels compared with TCMR. Bulging ICAM1-positive endothelial cells, morphology typical of endothelial activation, is shown in the inset. Granzyme B–positive cells were abundant in the allograft during TCMR but minimal during AMR. The staining was conducted in biopsies collected during the suspected AMR episode and each of the 4 episodes of TCMR. Original magnification, ×20 (first and third columns); ×40 (second and fourth columns); ×100 (inset).