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Endothelial molecules decipher the mechanisms and functional pathways in antibody-mediated rejection

Authors
Journal
Human Immunology
0198-8859
Publisher
Elsevier
Volume
73
Issue
12
Identifiers
DOI: 10.1016/j.humimm.2012.07.332
Keywords
  • Endothelial Cell
  • Gene Expression
  • Rejection
  • Antibody
  • Transplantation
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Microvascular endothelium is the main target of injury in antibody-mediated rejection of human organ transplants. Hence, antibody-mediated rejection histologically presents with microvascular inflammation (pulmonary or myocardial or peritubular capillaritis, glomerulitis), thrombosis, and endothelial remodeling (duplication and/or multilayering of glomerular and capillary basement membranes). We previously observed upregulation of several endothelial genes in kidney transplant biopsies from patients with donor specific antibodies, indicating active antibody-mediated rejection and poor graft survival. Furthermore, endothelial molecular signals discovered a previously unknown clinical phenotype: C4d negative antibody-mediated rejection. With the recognition of C4d negative antibody-mediated rejection, data from multiple transplant centers now show that antibody-mediated rejection is the most common cause of late kidney transplant failure. This paper reviews the current understanding of endothelial cell biology in antibody-mediated rejection, emphasizing recent advances and pending questions. Furthermore, the paper discusses functionally active pathways in human antibody-mediated rejection, which include aspects of endothelial activation with increased endothelial adhesive and pro-coagulant signals facilitating leukocyte trafficking and attachment, cell-to-basement membrane interactions, platelet activation, coagulation, and endothelial repair responses. To understand effector mechanisms of antibody-mediated rejection and quantify the degree of antibody-mediated tissue injury in clinical transplants, endothelial cells provide a useful read-out.

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