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Belatacept

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https://www.readbyqxmd.com/read/29672443/belatacept-and-auto-immune-adverse-events
#1
Simon Ville, Diego Cantarovich
No abstract text is available yet for this article.
April 18, 2018: Transplantation
https://www.readbyqxmd.com/read/29594146/early-conversion-from-tacrolimus-to-belatacept-in-a-highly-sensitized-renal-allograft-recipient-with-calcineurin-inhibitor-induced-de-novo-post-transplant-hemolytic-uremic-syndrome
#2
Vasishta S Tatapudi, Bonnie E Lonze, Ming Wu, Robert A Montgomery
Background: Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI)-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this...
January 2018: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/29573335/posttransplant-reduction-in-pre-existing-donor-specific-antibody-levels-after-belatacept-vs-cyclosporine-based-immunosuppression-post-hoc-analyses-of-benefit-and-benefit-ext
#3
R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen
BENEFIT and BENEFIT-EXT were phase III studies of cytotoxic T-cell crossmatch-negative kidney transplant recipients randomized to belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression. Following study completion, presence/absence of HLA-specific antibodies was determined centrally via solid-phase flow cytometry screening. Stored sera from anti-HLA-positive patients were further tested with a single-antigen bead assay to determine antibody specificities, presence/absence of donor-specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present...
March 24, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29570163/conversion-to-belatacept-in-maintenance-kidney-transplant-patients-a-retrospective-multicenter-european-study
#4
Amandine Darres, Camillo Ulloa, Susanne Brakemeier, Cyril Garrouste, Oriol Bestard, Arnaud Del Bello, Rebecca Sberro Soussan, Michael Dürr, Klemens Budde, Christophe Legendre, Nassim Kamar
BACKGROUND: The use of belatacept is not yet approved for maintenance kidney-transplant patients. This retrospective multicenter European study aimed to assess the efficacy and safety of conversion to belatacept in a large cohort of patients in a real-life setting, and to identify the predictive factors for improved kidney function after the switch. METHODS: Two-hundred and nineteen maintenance kidney-transplant patients from 5 European kidney-transplant centers were converted to belatacept at 21...
March 22, 2018: Transplantation
https://www.readbyqxmd.com/read/29569634/response-commentary-belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#5
COMMENT
Carla C Baan, Gretchen N de Graav, Willem Weimar, Dennis A Hesselink
No abstract text is available yet for this article.
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29509571/fulminant-acute-respiratory-distress-syndrome-after-calcineurin-inhibitor-belatacept-conversion-in-a-lung-transplant-recipient
#6
Olivier Brugière, Aurelie Cazes, Laure Champion, MArie-Pierre Debray, Gisèle Mourin, Bruno Crestani, Deborah Sroussi, Vincent Bunel, Gilles Jebrak, Gaëlle Dauriat, Yves Castier, Pierre Mordant, Brice Lortat-Jacob, Sylvain Jean-Baptiste, Lila Bouadma, Hervé Mal, Gabriel Thabut
No abstract text is available yet for this article.
March 5, 2018: Transplantation
https://www.readbyqxmd.com/read/29509295/de-novo-donor-specific-antibodies-in-belatacept-treated-vs-cyclosporine-treated-kidney-transplant-recipients-post-hoc-analyses-of-the-randomized-phase-iii-benefit-and-benefit-ext-studies
#7
R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen
Donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection and graft failure. In BENEFIT and BENEFIT-EXT, kidney transplant recipients were randomized to receive belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression for up to 7 years (84 months). The presence/absence of HLA-specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid-phase flow cytometry screening...
March 6, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29461660/outcomes-at-7-years-post-transplant-in-black-versus-non-black-kidney-transplant-recipients-administered-belatacept-or-cyclosporine-in-benefit-and-benefit-ext
#8
Sander Florman, Flavio Vincenti, Antoine Durrbach, Marwan Abouljoud, Barbara Bresnahan, Valter Duro Garcia, Laura Mulloy, Kim Rice, Lionel Rostaing, Carlos Zayas, Kellie Calderon, Ulf Meier-Kriesche, Martin Polinsky, Lingfeng Yang, Jose Medina Pestana, Christian P Larsen
Clinical outcomes are generally worse for black versus non-black renal allograft recipients. In BENEFIT and BENEFIT-EXT, recipients were randomized to belatacept more-intense-based, belatacept less-intense-based, or cyclosporine-based immunosuppression. At year 7, belatacept was associated with superior graft survival versus cyclosporine in BENEFIT (recipients of living or standard criteria deceased donor kidneys); belatacept was associated with similar graft survival versus cyclosporine in BENEFIT-EXT (recipients of extended criteria donor kidneys)...
February 20, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29358873/stricturing-crohn-s-disease-like-colitis-in-a-patient-treated-with-belatacept
#9
Anne Bozon, Guillaume Jeantet, Benjamin Rivière, Natalie Funakoshi, Gaspard Dufour, Roman Combes, Jean-Christophe Valats, Sylvie Delmas, Jean Emmanuel Serre, Michael Bismuth, Jeanne Ramos, Moglie Le Quintrec, Pierre Blanc, Guillaume Pineton de Chambrun
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn's disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.
December 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29321374/selective-cd28-blockade-attenuates-ctla-4-dependent-cd8-memory-t-cell-effector-function-and-prolongs-graft-survival
#10
Danya Liu, I Raul Badell, Mandy L Ford
Memory T cells pose a significant problem to successful therapeutic control of unwanted immune responses during autoimmunity and transplantation, as they are differentially controlled by cosignaling receptors such as CD28 and CTLA-4. Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80 and CD86, but they also have the unintended consequence of blocking the ligands for CTLA-4, a process that may inadvertently boost effector responses. Here, we show that a potentially novel anti-CD28 domain antibody (dAb) that selectively blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival in sensitized recipients as compared with CTLA-4 Ig...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29321143/control-of-humoral-response-in-renal-transplantation-by-belatacept-depends-on-a-direct-effect-on-b-cells-and-impaired-t-follicular-helper-b-cell-crosstalk
#11
Claire Leibler, Allan Thiolat, Carole Hénique, Chloé Samson, Caroline Pilon, Marie Tamagne, France Pirenne, Benoit Vingert, José L Cohen, Philippe Grimbert
Generation of de novo donor-specific antibodies ( dn DSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dn DSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dn DSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated...
March 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29309803/effect-of-cyclosporine-tacrolimus-and-sirolimus-on-cellular-senescence-in-renal-epithelial-cells
#12
Christian Koppelstaetter, Georg Kern, Gisela Leierer, Sabine Maria Mair, Gert Mayer, Johannes Leierer
INTRODUCTION: In transplantation medicine calcineurin inhibitors (CNI) still represent the backbone of immunosuppressive therapy. The nephrotoxic potential of the CNI Cyclosporine A (CsA) and Tacrolimus (FK506) is well recognized and CNI not only have been linked with toxicity, but also with cellular senescence which hinders parenchymal tissue regeneration and thus may prime kidneys for subsequent insults. To minimize pathological effects on kidney grafts, alternative immunosuppressive agents like mTOR inhibitors or the T-cell co-stimulation blocker Belatacept have been introduced...
April 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#13
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) after an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine antithymocyte globulin (Atgam) and donor bone marrow transplantation (DBMT). Because these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
April 2018: Transplantation
https://www.readbyqxmd.com/read/29225802/effective-immunosuppressive-management-with-belatacept-and-eculizumab-in-post-transplant-ahus-due-to-a-homozygous-deletion-of-cfhr1-cfhr3-and-the-presence-of-cfh-antibodies
#14
Johannes Münch, Anette Bachmann, Maik Grohmann, Christof Mayer, Michael Kirschfink, Tom H Lindner, Carsten Bergmann, Jan Halbritter
Atypical haemolytic uraemic syndrome (aHUS) may clinically present as acute renal graft failure resulting from excessive activation of the complement cascade. While mutations of complement-encoding genes predispose for aHUS, it is generally thought to require an additional insult (e.g. drugs) to trigger and manifest the full-blown clinical syndrome. Calcineurin inhibitors (CNIs) used for immunosuppression act as potential triggers, especially in the post-transplantation setting. Therefore, CNI-free immunosuppressive regimens may be beneficial...
December 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29218048/commentary-belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#15
COMMENT
Paul M Schroder, Brian Ezekian, Mandy Ford, Stuart J Knechtle, Jean Kwun
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29157988/de-novo-thrombotic-microangiopathy-after-kidney-transplantation
#16
REVIEW
Neetika Garg, Helmut G Rennke, Martha Pavlakis, Kambiz Zandi-Nejad
Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS...
January 2018: Transplantation Reviews
https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-postdepletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#17
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevent CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable than more naive phenotypes of repopulating postdepletion, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29123208/differential-t-cell-signaling-pathway-activation-by-tacrolimus-and-belatacept-after-kidney-transplantation-post-hoc-analysis-of-a-randomised-controlled-trial
#18
Nynke M Kannegieter, Dennis A Hesselink, Marjolein Dieterich, Gretchen N de Graav, Rens Kraaijeveld, Carla C Baan
Pharmacokinetic immunosuppressive drug monitoring poorly correlates with clinical outcomes after solid organ transplantation. A promising method for pharmacodynamic monitoring of tacrolimus (TAC) in T cell subsets of transplant recipients might be the measurement of (phosphorylated) p38MAPK, ERK1/2 and Akt (activated downstream of the T cell receptor) by phospho-specific flow cytometry. Here, blood samples from n = 40 kidney transplant recipients (treated with either TAC-based or belatacept (BELA)-based immunosuppressive drug therapy) were monitored before and throughout the first year after transplantation...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084026/cause-for-cautious-optimism-belatacept-for-patients-with-impaired-kidney-allograft-function
#19
John S Gill
No abstract text is available yet for this article.
March 2018: Transplantation
https://www.readbyqxmd.com/read/29077658/early-conversion-to-belatacept-in-kidney-transplant-recipient-with-low-glomerular-filtration-rate
#20
Dina Abdelwahab Elhamahmi, Raymond L Heilman, Byron Smith, Janna Huskey, Hasan Khamash, Bruce Kaplan
BACKGROUND: Our aim was to determine the impact of converting from tacrolimus to belatacept in patients with stable low eGFR early after kidney transplant. METHODS: This is a single center retrospective case control study. During this study period we had a clinical protocol to convert patients to belatacept if they had a stable but low GFR and they were at least 1-month posttransplant. Eligible patients had stable but low eGFR usually < 40 ml/min/1.73m2. We used direct matching to select 1 control case for each patient converted to belatacept...
October 26, 2017: Transplantation
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