Insights from immunoproteomic profiling of a rejected full-face transplant.

Abstract

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.

• Authors: Catherine A A Lee, Diana Wang, Martin Kauke-Navarro, Eleanor Russell-Goldman, Shuyun Xu, Kyla N Mucciarone, Sadaf Sohrabi, Christine G Lian, Bohdan Pomahac, George F Murphy
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 23 Issue 7 Pg. 1058-1061 (07 2023) ISSN: 1600-6143 [Electronic] United States
• PMID: 37037378 (Publication Type: Case Reports, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.

Topics

• Facial Transplantation
• Graft Survival
• Proteomics
• Vascularized Composite Allotransplantation
• Composite Tissue Allografts (transplantation)
• Graft Rejection (etiology, pathology)