Donor-specific Immune Senescence as a Candidate Biomarker of Operational Tolerance Following Liver Transplantation in Adults: Results of a Prospective, Multicenter Cohort Study.
Naoki Tanimine, James F Markmann, Michelle A Wood-Trageser, Anthony J Demetris, Kristen Mason, Juliete A F Silva, Josh Levitsky, Sandy Feng, Abhinav Humar, Jean C Emond, Abraham Shaked, Goran Klintmalm, Alberto Sanchez-Fueyo, Drew Lesniak, Cynthia P Breeden, Gerald T Nepom, Nancy D Bridges, Julia Goldstein, Christian P Larsen, Michele DesMarais, Geo Gaile, Sindhu Chandran
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引用次数: 0
Abstract
Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in non-autoimmune, non-viral adult liver transplant recipients. Enrolled subjects were ≥3 years post-transplant with minimal/absent inflammation or fibrosis on a screening liver biopsy. The primary endpoint was operational tolerance at 52 weeks following complete ISW. Of 61 subjects who initiated ISW, 34 failed during ISW and 10 restarted immunosuppression due to clinically manifest acute rejection. Of the 17 subjects remaining off immunosuppression at 1 year, 10 were ultimately deemed tolerant by biopsy. There were no cases of chronic rejection or graft loss. The majority of subjects (78.6%), including those who experienced rejection, ended the study on same or less calcineurin inhibitor than at baseline. 28.3% developed de novo DSA during ISW, which persisted in 11.3%. A minority (16.4%) of histologically and clinically stable long-term adult liver transplant recipients can successfully discontinue and remain off immunosuppression. Increased frequency of donor-specific T cell senescence, C4d deposition and higher density of immune synapses on the screening liver biopsy emerged as potential candidate biomarkers for operational tolerance. NCT02533180.
期刊介绍:
The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide.
The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.