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Belatacept

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https://www.readbyqxmd.com/read/29027667/co-inhibitory-profile-and-cytotoxicity-of-cd57-pd-1-t-cells-in-end-stage-renal-disease-patients
#1
Rens Kraaijeveld, Gretchen N de Graav, Marjolein Dieterich, Nicolle H R Litjens, Dennis A Hesselink, Carla C Baan
Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection as compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28(-) T-cells, which express CD57, are not susceptible to belatacept treatment. High number of CD4(+) CD57(+) PD-1(-) T-cells pre transplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of FACS-sorted CD4(+) CD57(+) PD-1(-) and CD8(+) CD57(+) PD-1(-) T-cells, and their CD57(-) control populations, after allo antigen stimulation...
October 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28970838/successful-treatment-of-t-cell-mediated-acute-rejection-with-delayed-ctla4-ig-in-mice
#2
James S Young, Stella H-W Khiew, Jinghui Yang, Augustin Vannier, Dengping Yin, Roger Sciammas, Maria-Luisa Alegre, Anita S Chong
Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28923620/late-conversion-to-belatacept-after-kidney-transplantation-outcome-and-prognostic-factors
#3
M Dürr, N Lachmann, B Zukunft, D Schmidt, K Budde, S Brakemeier
BACKGROUND: Conversion to belatacept at a later point after kidney transplantation (KT) as a rescue therapy has been shown to be beneficiary in an increasing number of patients, but prognostic factors for a favorable outcome have never been investigated. METHODS: The present study analyzed all KT patients after late conversion to belatacept in a single center regarding graft survival and changes in estimated glomerular filtration rate (eGFR), proteinuria, and mean fluorescence intensity (MFI) of donor-specific antibodies (DSA)...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28873970/immunosuppressive-agents-in-adult-kidney-transplantation-in-the-national-health-service-a-model-based-economic-evaluation
#4
Tristan M Snowsill, Jason Moore, Ruben E Mujica Mota, Jaime L Peters, Tracey L Jones-Hughes, Nicola J Huxley, Helen F Coelho, Marcela Haasova, Chris Cooper, Jenny A Lowe, Jo L Varley-Campbell, Louise Crathorne, Matt J Allwood, Rob Anderson
Background: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. Methods: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime...
July 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28805142/intravenous-immunoglobulins-modify-relapsing-membranous-glomerulonephritis-after-kidney-transplantation-a-case-report
#5
Sanne Steyaert, Jo Van Dorpe, Anne Hoorens, Wim Van Biesen, Steven Van Laecke
OBJECTIVES: Recurrence of membranous glomerulonephritis after transplant is common and is an important cause of loss of renal graft. This case supports the effect of immunoglobulins in the treatment of this disease after transplantation. It is the first report in the literature with a follow-up of more than 10 years and because of the sustained effect of the immunoglobulins, it strengthens the idea that this can alter long-term outcome. METHODS: Single case study and search of the literature...
August 14, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28758341/ten-year-outcomes-in-a-randomized-phase-ii-study-of-kidney-transplant-recipients-administered-belatacept-4-weekly-or-8-weekly
#6
F Vincenti, G Blancho, A Durrbach, G Grannas, J Grinyó, H-U Meier-Kriesche, M Polinsky, L Yang, C P Larsen
In the phase II IM103-100 study, kidney transplant recipients were first randomized to belatacept more-intensive-based (n = 74), belatacept less-intensive-based (n = 71), or cyclosporine-based (n = 73) immunosuppression. At 3-6 months posttransplant, belatacept-treated patients were re-randomized to receive belatacept every 4 weeks (4-weekly, n = 62) or every 8 weeks (8-weekly, n = 60). Patients initially randomized to cyclosporine continued to receive cyclosporine-based immunosuppression. Cumulative rates of biopsy-proven acute rejection (BPAR) from first randomization to year 10 were 22...
July 31, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28742936/benefits-and-limitations-of-belatacept-in-4-hand-transplanted-patients
#7
J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (CTLA4Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor specific antibodies (DSA) make it an interesting agent in hand transplantation. In order to reduce CNI immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand transplanted patients at month 4, at 6, 9, and 13 years after hand/forearm transplantation. Patients received 5mg/kg belatacept every 2 weeks, the dosing interval was extended to 4 weeks after 5 applications...
July 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#8
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
BACKGROUND: Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. METHODS: Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28708266/belatacept-conversion-in-an-hiv-positive-kidney-transplant-recipient-following-anti-thymocyte-globulin-induction
#9
Samantha A Kuten, Samir J Patel, Ashvin Baru, A Osama Gaber, Rustin D Crutchley, Venkataraman Ramanathan, Richard J Knight
Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction...
July 14, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28707779/belatacept-rescue-therapy-in-kidney-transplant-recipients-with-vascular-lesions-a-case-control-study
#10
D Bertrand, L Cheddani, I Etienne, A François, M Hanoy, C Laurent, L Lebourg, F Le Roy, L Lelandais, M C Loron, M Godin, D Guerrot
Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context. We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6...
July 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28691954/maintenance-belatacept-based-immunosuppression-in-lung-transplantation-recipients-who-failed-calcineurin-inhibitors
#11
Carlo J Iasella, Ryan J Winstead, Cody A Moore, Bruce A Johnson, Ayelet T Feinberg, Matthew R Morrell, J W Awori Hayanga, Elizabeth A Lendermon, Adriana Zeevi, John F McDyer, Christopher R Ensor
BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR...
July 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28677367/neurologic-complications-in-kidney-transplant-recipients
#12
Piotr C Piotrowski, Anna Lutkowska, Alexander Tsibulski, Marek Karczewski, Paweł P Jagodziński
<i>Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28662293/retrospective-evaluation-of-the-efficacy-and-safety-of-belatacept-with-thymoglobulin-induction-and-maintenance-everolimus-a-single-center-clinical-experience
#13
David Wojciechowski, Sindhu Chandran, Joshua Y C Yang, Minnie M Sarwal, Flavio Vincenti
Belatacept use has been constrained by higher rates of acute rejection. We hypothesized that belatacept with low-dose rATG and initial mycophenolate maintenance with conversion to everolimus at 1 month post-transplant ± corticosteroids would improve efficacy and maintain safety. Retrospective single-center analysis of the first 44 low immunologic risk kidney transplant recipients treated with this regimen. The cohort was 59% male, mean age at transplant of 57 years. Diabetes was the most common cause of ESRD (39%)...
September 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28638849/refractory-t-cell-anergy-and-rapidly-fatal-progressive-multifocal-leukoencephalopathy-after-prolonged-ctla4-therapy
#14
Manon Dekeyser, Marie-Ghislaine de Goër de Herve, Houria Hendel-Chavez, Céline Labeyrie, David Adams, Ghaïdaa Adebs Nasser, Jacques Gasnault, Antoine Durrbach, Yassine Taoufik
Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease due to central nervous system replication of the human polyomavirus JC virus (JCV) in immunosuppressed patients. The only effective therapeutic approach is to restore anti-JCV T-cell responses. In this study, we describe a case of rapidly fatal PML with JCV T-cell anergy in a renal transplant patient treated with CTLA4-Ig (belatacept, a CD28-B7 costimulation blocker and T-cell anergy inducer). T-cell anergy could not be reversed despite several therapeutic approaches...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#15
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28613437/t-cell-subsets-predicting-belatacept-resistant-rejection-finding-the-root-where-the-trouble-starts
#16
EDITORIAL
T Wekerle
No abstract text is available yet for this article.
September 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28580358/belatacept-as-an-alternative-to-calcineurin-inhibitors-in-patients-with-solid-organ-transplants
#17
REVIEW
Dhiren Kumar, Spencer LeCorchick, Gaurav Gupta
The goal of immunosuppression in transplantation has shifted to improving long-term outcomes, reducing drug-induced toxicities while preserving the already excellent short-term outcomes. Long-term gains in solid organ transplantation have been limited at least partly due to the nephrotoxicity and metabolic side effects of calcineurin inhibitors (CNIs). The alloimmune response requires activation of the costimulatory pathway for T cell proliferation and amplification. Belatacept is a molecule that selectively blocks T cell costimulation...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28556519/lessons-learned-early-termination-of-a-randomized-trial-of-calcineurin-inhibitor-and-corticosteroid-avoidance-using-belatacept
#18
K A Newell, A K Mehta, C P Larsen, P G Stock, A B Farris, S G Mehta, D Ikle, B Armstrong, Y Morrison, N Bridges, M Robien, R B Mannon
The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively...
October 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#19
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus-based protocol (n = 205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28540602/late-conversion-from-tacrolimus-to-a-belatacept-based-immuno-suppression-regime-in-kidney-transplant-recipients-improves-renal-function-acid-base-derangement-and-mineral-bone-metabolism
#20
Kevin Schulte, Clara Vollmer, Vera Klasen, Jan Hinrich Bräsen, Jodok Püchel, Christoph Borzikowsky, Ulrich Kunzendorf, Thorsten Feldkamp
BACKGROUND: Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients. METHODS: In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function...
August 2017: Journal of Nephrology
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