ArticleFrontiers in immunology2021
Defining a Methylation Signature Associated With Operational Tolerance in Kidney Transplant Recipients.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review.Clinical epigenetics · 2022Pooled it
- Epigenetic regulation in transplant rejection and tolerance: mechanisms and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice.Journal of inflammation research · 2025Article
- Review
- Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant.Kidney international reports · 2023Article
- An exome-wide study of renal operational tolerance.Frontiers in medicine · 2022Article
- Epigenetic Regulation in Kidney Transplantation.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Operational tolerance after kidney transplantation is defined as stable graft acceptance without the need for immunosuppression therapy. However, it is not clear which cellular and molecular pathways are driving tolerance in these patients. We performed genome-wide analysis of DNA methylation in peripheral blood mononuclear cells from kidney transplant recipients with chronic rejection and operational tolerance from the Genetic Analysis of Molecular Biomarkers of Immunological Tolerance (GAMBIT) study. Our results showed that both clinical stages diverge in 2737 genes, indicating that each one has a specific methylation signature associated with transplant outcome. We also observed that tolerance is associated with demethylation in genes involved in immune function, including B and T cell activation and Th17 differentiation, while in chronic rejection it is associated with intracellular signaling and ubiquitination pathways. Using co-expression network analysis, we selected 12 genomic regions that are specifically hypomethylated or hypermethylated in tolerant patients. Analysis of these genes in transplanted patients with low dose of steroids showed that these have a similar methylation signature to that of tolerant recipients. Overall, these results demonstrate that methylation analysis can mirror the immune status associated with transplant outcome and provides a starting point for understanding the epigenetic mechanisms associated with tolerance.
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Registered trials
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