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Lookup NU author(s): Dr Steven MassonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning. One hundred sixteen adult stable liver transplant recipients were randomized 1:1 to either arm A (IS withdrawal regardless of biomarker status) or arm B (IS withdrawal in biomarker-positive recipients). Immunosuppression withdrawal was initiated in 82 participants, rejection occurred in 54 (67.5%), and successful discontinuation of IS was achieved in 22 (27.5%), but only 13 (16.3%) met operational tolerance histologic criteria (10 in arm A; 3 in arm B). The biomarker test did not yield useful information in selecting patients able to successfully discontinue IS. Operational tolerance was associated with time posttransplant, recipient age, presence of circulating exhausted CD8+ T cells, and a reduced number of immune synapses within the graft.
Author(s): Vionnet J, Torres-Yaguana J, Miquel R, Abraldes JG, Wall J, Kodela E, Lozano J-J, Ruiz P, Navasa M, Marshall A, Nevens F, Gelson W, Leithead J, Masson S, Jaeckel E, Taubert R, Tachtatzis P, Eurich D, Simpson KJ, Bonaccorsi-Riani E, Ferguson J, Quaglia A, Demetris AJ, Lesniak AJ, Elstad M, Delord M, Douiri A, Rebollo-Mesa I, Martinez-Llordella M, Silva JAF, Markmann JF, Sanchez-Fueyo A
Publication type: Article
Publication status: Published
Journal: American Journal of Transplantation
Year: 2025
Pages: epub ahead of print
Online publication date: 17/12/2024
Acceptance date: 28/02/2024
Date deposited: 21/01/2025
ISSN (print): 1600-6135
ISSN (electronic): 1600-6143
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.ajt.2024.12.002
DOI: 10.1016/j.ajt.2024.12.002
Data Access Statement: To ensure the privacy of the participants, further research data remain confidential. The anonymized data set is available upon request.
PubMed id: 39706366
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