Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression
Vionnet, Julien Torres-Yaguana, Jorge Miquel, Rosa Abraldes, Juan G Wall, Jurate Kodela, Elisavet Lozano, Juan-Jose Ruiz, Pablo Navasa, Miguel Marshall, Aileen
Vionnet, Julien
Torres-Yaguana, Jorge
Miquel, Rosa
Abraldes, Juan G
Wall, Jurate
Kodela, Elisavet
Lozano, Juan-Jose
Ruiz, Pablo
Navasa, Miguel
Marshall, Aileen
Affiliation
King's College London University; King's College Hospital NHS Foundation Trust; University Hospital of Lausanne; University of Alberta; Instituto de Salud Carlos III; University of Barcelona; Royal Free London NHS Foundation Trust; University Hospital Leuven; Cambridge University Hospitals NHS Foundation Trust; Newcastle upon Tyne Hospitals NHS Foundation Trust; Newcastle University; Hannover Medical School; Leeds Teaching Hospitals NHS Trust; Charité Hospital Berlin; NHS Lothian; Cliniques Universitaires St-Luc; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; University of Pittsburgh; Quell Therapeutics Ltd; Immune Tolerance Network Seattle; Emory University; University of Pennsylvania
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Publication date
2024-12-18
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Abstract
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.
Citation
Vionnet J, Torres-Yaguana J, Miquel R, Abraldes JG, Wall J, Kodela E, Lozano JJ, 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, Sánchez-Fueyo A. Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression. Am J Transplant. 2025 May;25(5):1045-1058. doi: 10.1016/j.ajt.2024.12.002. Epub 2024 Dec 18.
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Article