New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.

Autor:	Franco-Acevedo A; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, United States., Comes J; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands., Mack JJ; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA, United States., Valenzuela NM; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in transplantation [Front Transplant] 2023 Apr 28; Vol. 2, pp. 1146040. Date of Electronic Publication: 2023 Apr 28 (Print Publication: 2023).
DOI:	10.3389/frtra.2023.1146040
Abstrakt:	Transplant vasculopathy (TV) causes thickening of donor blood vessels in transplanted organs, and is a significant cause of graft loss and mortality in allograft recipients. It is known that patients with repeated acute rejection and/or donor specific antibodies are predisposed to TV. Nevertheless, the exact molecular mechanisms by which alloimmune injury culminates in this disease have not been fully delineated. As a result of this incomplete knowledge, there is currently a lack of effective therapies for this disease. The immediate intracellular signaling and the acute effects elicited by anti-donor HLA antibodies are well-described and continuing to be revealed in deeper detail. Further, advances in rejection diagnostics, including intragraft gene expression, provide clues to the inflammatory changes within allografts. However, mechanisms linking these events with long-term outcomes, particularly the maladaptive vascular remodeling seen in transplant vasculopathy, are still being delineated. New evidence demonstrates alterations in non-coding RNA profiles and the occurrence of endothelial to mesenchymal transition (EndMT) during acute antibody-mediated graft injury. EndMT is also readily apparent in numerous settings of non-transplant intimal hyperplasia, and lessons can be learned from advances in those fields. This review will provide an update on these recent developments and remaining questions in our understanding of HLA antibody-induced vascular damage, framed within a broader consideration of manifestations and implications across transplanted organ types. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Franco-Acevedo, Comes, Mack and Valenzuela.)
Databáze:	MEDLINE
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