Win Thet Su, Murakami Naoka, Borges Thiago J, Chandraker Anil, Murphy George, Lian Christine, Barrera Victor, Ho Sui Shannan, Schoenfeld David, Teague Jessica, Bueno Ericka, Tullius Stefan G, Pomahac Bohdan, Clark Rachael A, Riella Leonardo V
Division of Plastic Surgery, Department of Surgery.
Department of Dermatology.
JCI Insight. 2017 Jul 6;2(13). doi: 10.1172/jci.insight.93894.
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.
超过80%的面部移植会发生排斥反应,但目前尚未建立面部移植后抗体介导排斥反应(AMR)的诊断标准。鉴于应对AMR和T细胞介导排斥反应(TCMR)需要不同的治疗策略,因此迫切需要明确能够区分这两种同种免疫反应的特征。在此,我们报告了对我们认为是首例且唯一的交叉配型阳性面部移植高敏受者移植后长达4年的纵向免疫学检查。我们对在疑似AMR和TCMR发作期间以及5个非排斥时间点采集的同种异体移植活检组织进行了基因表达谱分析。我们的数据表明,AMR具有独特的分子特征,其特点是内皮相关基因(包括ICAM1、VCAM1和SELE)过度表达。尽管我们的研究结果仅限于一名患者,但这些发现凸显了开发和应用分子标志物以区分AMR与TCMR从而指导临床管理的潜在重要性。此外,我们的病例表明,对同种异体移植活检组织进行分子评估有可能为排斥反应的潜在机制提供新的见解。最后,我们的中期结果表明,术前交叉配型阳性的高敏患者进行面部移植是可行且可管理的。