ArticleJournal of the American Society of Nephrology : JASN2016
Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft Rejection.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- The Inhibition of CD40/CD154 Costimulatory Signaling in the Prevention of Renal Transplant Rejection in Nonhuman Primates: A Systematic Review and Meta Analysis.Frontiers in immunology · 2022Pooled it
- Trial
- Abatacept Targets T Follicular Helper and Regulatory T Cells, Disrupting Molecular Pathways That Regulate Their Proliferation and Maintenance.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Review
- Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?Journal of personalized medicine · 2024Review
- Innovative immunosuppression in kidney transplantation: A challenge for unmet needs.World journal of transplantation · 2022Review
- Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.Trends in molecular medicine · 2022Review
- Targeting T Follicular Helper Cells to Control Humoral Allogeneic Immunity.Transplantation · 2021Review
- Superior inhibition of alloantibody responses with selective CD28 blockade is CTLA-4 dependent and T follicular helper cell specific.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- The impact of belatacept on the phenotypic heterogeneity of renal T cell-mediated alloimmune response: The critical role of maintenance treatment and inflammatory load.Clinical transplantation · 2020Article
- The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival.Translational andrology and urology · 2020Article
- Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2020Article
- Review
- Belatacept and CD28 Costimulation Blockade: Preventing and Reducing Alloantibodies over the Long Term.Current transplantation reports · 2019Article
- The past, present, and future of costimulation blockade in organ transplantation.Current opinion in organ transplantation · 2019Review
- Transplant research in nonhuman primates to evaluate clinically relevant immune strategies in organ transplantation.Transplantation reviews (Orlando, Fla.) · 2019Review
- High Dimensional Renal Profiling: Towards a Better Understanding or Renal Transplant Immune Suppression.Current transplantation reports · 2019Article
- Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis inBioMed research international · 2019Article
- CXCR5Frontiers in immunology · 2019Article
- CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates.The Journal of clinical investigation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Belatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab' antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid-resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell-specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preexisting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.
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Registered trials
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.