Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Am J Transplant. 2023 Jul;23(7):1058-1061. doi: 10.1016/j.ajt.2023.04.008. Epub 2023 Apr 8.
Vascularized composite allografts (VCAs) of faces and extremities are subject to chronic rejection that is incompletely understood. Here we report on immunoproteomic evaluation of a full facial VCA removed 88 months after transplantation due to chronic rejection. CD8-positive T cells of donor (graft) origin infiltrate deep intragraft arteries in apposition to degenerating endothelium of chimeric recipient origin in association with arteriosclerotic alterations. Digital spatial proteomic profiling highlighted proteins expressed by activated cytotoxic T cells and macrophages as well as pathway components involved in atherogenic responses, including Indoleamine 2,3-Dioxygenase 1 (IDO1) and Stimulator of Interferon Response CGAMP Interactor (STING). Chronic facial VCA rejection thus involves T cell/macrophage-mediated accelerated arteriosclerosis not normally represented in punch biopsies and potentially driven by persistent graft-resident effector T cells and recipient target endothelium that chimerically repopulates graft arteries.
血管化复合同种异体移植物（VCAs）的面部和四肢会发生慢性排斥反应，但这种反应的机制尚不完全清楚。本研究报告了一例因慢性排斥反应而在移植后 88 个月被切除的全颜面 VCA 的免疫蛋白质组学评估。供体（移植物）来源的 CD8+T 细胞浸润到深在的移植物内动脉中，与嵌合受者来源的退化内皮细胞并列，同时伴有动脉粥样硬化改变。数字空间蛋白质组学分析突出了表达在活化的细胞毒性 T 细胞和巨噬细胞中的蛋白质，以及参与动脉粥样硬化反应的途径成分，包括吲哚胺 2,3-双加氧酶 1（IDO1）和干扰素反应 CGAMP 相互作用因子（STING）。因此，慢性面部 VCA 排斥反应涉及 T 细胞/巨噬细胞介导的加速动脉粥样硬化，这种变化在穿刺活检中通常不会表现出来，并且可能是由持续存在的移植物驻留效应 T 细胞和嵌合再殖移植物动脉的受者靶内皮细胞驱动的。
