Trial reportHepatology (Baltimore, Md.)2013
Systemic immunoregulatory and proteogenomic effects of tacrolimus to sirolimus conversion in liver transplant recipients.
Trial report in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Proteomics in Liver Transplantation: A Systematic Review.Frontiers in immunology · 2021Pooled it
- Trial
- Effect of Qingfei Mixture () on pediatric mycoplasma pneumoniae pneumonia with phlegm heat obstructing Fei (Lung) syndrome.Chinese journal of integrative medicine · 2017Trial
- Trial
- B-Cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease.The Journal of pediatrics · 2013Trial
- Identification of urinary metabolites correlated with tacrolimus levels through high-precision liquid chromatography-mass spectrometry and machine learning algorithms in kidney transplant patients.Medicine and pharmacy reports · 2025Article
- Hepatic Manifestations Following Gene Therapy.Gastro hep advances · 2025Review
- Advancing immunosuppression in liver transplantation: the role of regulatory T cells in immune modulation and graft tolerance.Clinical transplantation and research · 2024Review
- Challenges with sirolimus experimental data to inform QSP model of post-transplantation cyclophosphamide regimens.Clinical and translational science · 2024Review
- Metabolic Reprograming of Macrophages: A New Direction in Traditional Chinese Medicine for Treating Liver Failure.Journal of immunology research · 2024Review
- Achieving tolerance modifies cancer susceptibility profiles in liver transplant recipients.Cancer medicine · 2023Article
- Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring.Frontiers in pharmacology · 2023Review
- mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis.Frontiers in immunology · 2022Article
- Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation.Frontiers in immunology · 2022Review
- Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis.Biomedical journal · 2021Article
- Donor-derived regulatory dendritic cell infusion results in host cell cross-dressing and T cell subset changes in prospective living donor liver transplant recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Immunosuppression Withdrawal in Liver Transplant Recipients on Sirolimus.Hepatology (Baltimore, Md.) · 2020Article
- Essential updates 2018/2019: Liver transplantation.Annals of gastroenterological surgery · 2020Review
- Translational medical research and liver transplantation: systematic review.Translational gastroenterology and hepatology · 2018Review
- Analysis of long term CD4+CD25highCD127- T-reg cells kinetics in peripheral blood of lung transplant recipients.BMC pulmonary medicine · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledImmunosuppression (IS) withdrawal from calcineurin inhibitors is only possible in ≈ 20% of liver transplant recipients. However, mammalian target of rapamycin inhibitors (e.g., sirolimus; SRL) appear to be more immunoregulatory and might promote a tolerant state for withdrawal. Our aim was to determine whether systemic (i.e., blood, marrow, and allograft) signatures of immunoregulation are promoted by conversion from tacrolimus (TAC) to SRL. We therefore performed the following serial assays before and after SRL conversion in liver transplant recipients to test for enhanced markers of immunoregulation: (1) flow-cytometry immunophenotyping of peripheral blood mononuclear cells (PBMCs) and bone marrow aspirates for regulatory T cells (Tregs) (e.g., CD4(+) CD25(+++) FOXP3(+) ) and regulatory dendritic cells (DCregs) (immunoglobulin-like transcript 3(+) /4(+) ); (2) liver biopsy immunohistochemical staining (e.g., FOXP3:CD3 and CD4:CD8 ratios) and immunophenotyping of biopsy-derived Tregs after growth in culture; (3) effects of pre- versus postconversion sera on Treg generation in mixed lymphocyte reactions; (4) peripheral blood nonspecific CD4 responses; and (5) peripheral blood gene transcripts and proteomic profiles. We successfully converted 20 nonimmune, nonviremic recipients (age, 57.2 ± 8.0; 3.5 ± 2.1 years post-liver transplantation) from TAC to SRL for renal dysfunction. Our results demonstrated significant increases in Tregs in PBMCs and marrow and DCregs in PBMCs (P < 0.01) after conversion. In biopsy staining, FOXP3:CD3 and CD4:CD8 ratios were significantly higher after conversion and a number of biopsy cultures developed new or higher FOXP3(+) cell growth. Nonspecific CD4 responses did not change. Both pre- and postconversion sera inhibited mixed lymphocyte reactions, although only TAC sera suppressed Treg generation. Finally, 289 novel genes and 22 proteins, several important in immunoregulatory pathways, were expressed after conversion.
conclusionsTAC to SRL conversion increases systemic Tregs, DCregs, and immunoregulatory proteogenomic signatures in liver transplant recipients and may therefore facilitate IS minimization or withdrawal.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.