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Belatacept

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https://www.readbyqxmd.com/read/28434523/belatacept-where-the-benefits-outweigh-the-risk
#1
EDITORIAL
Hallvard Holdaas, Geir Mjøen, Alan G Jardine
No abstract text is available yet for this article.
May 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28403127/a-randomized-controlled-clinical-trial-comparing-belatacept-with-tacrolimus-after-de-novo-kidney-transplantation
#2
Gretchen de Graav, Carla C Baan, Marian C Clahsen-van Groningen, Rens Kraaijeveld, Marjolein Dieterich, Wenda Verschoor, Jan H von der Thusen, Dave L Roelen, Monique Cadogan, Jacqueline van de Wetering, Joost van Rosmalen, Wilem Weimar, Dennis A Hesselink
BACKGROUND: Belatacept, an inhibitor of the CD28-CD80/86 co-stimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but is associated with a higher acute rejection risk than ciclosporin. Thus, no biomarker for belatacept-resistant rejection has been validated. In this randomized controlled trial, acute rejection-rate was compared between belatacept- and tacrolimus-treated patients and immunological biomarkers for acute rejection were investigated...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28401625/fatal-case-of-cutaneous-sparing-oro-laryngeal-zoster-in-a-renal-transplant-recipient
#3
Elie Helou, Matthew Grant, Marie Landry, Xinyu Wu, Jon S Morrow, Maricar F Malinis
Herpesvirus infections in solid organ transplant (SOT) recipients are a significant cause of morbidity and mortality. We report a case of herpes zoster (HZ) in a kidney transplant recipient while receiving belatacept, a CTLA-4 inhibitor that prevents acute rejection. The patient presented with oropharyngolaryngeal mucosal lesions that subsequently disseminated resulting in pneumonitis and meningo-encephalitis. Very late-onset HZ can occur and can present atypically in SOT recipients. Delayed recognition and treatment may result in poor outcomes, as illustrated by this case...
April 12, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28376033/causes-and-consequences-of-the-worldwide-belatacept-shortage
#4
Steven Gabardi, Teun van Gelder
No abstract text is available yet for this article.
April 4, 2017: Transplantation
https://www.readbyqxmd.com/read/28363404/acute-antibody-mediated-rejection-following-sleeve-gastrectomy-in-a-kidney-transplant-recipient-treated-with-a-belatacept-mycophenolate-mofetil-based-therapy
#5
Jamale Rizkallah, Nassim Kamar, Arnaud Del Bello
No abstract text is available yet for this article.
February 24, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28316600/methylation-of-foxp3-tsdr-underlies-the-impaired-suppressive-function-of-tregs-from-long-term-belatacept-treated-kidney-transplant-patients
#6
Evelyn Katy Alvarez Salazar, Arimelek Cortés-Hernández, Germán Rodrigo Alemán-Muench, Josefina Alberú, Jesús R Rodríguez-Aguilera, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Eric Cuevas, Eduardo Mancilla-Urrea, María Pérez García, Guillermo Mondragón-Ramírez, Mario Vilatobá, Ian Bostock, Erick Hernández-Méndez, David De Rungs, Eduardo A García-Zepeda, Gloria Soldevila
Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplanted patients remains controversial. Here, we analyzed the phenotype, function, and the epigenetic status of the Treg-specific demethylated region (TSDR) in FOXP3 of circulating Tregs from long-term kidney transplant patients under BLT or Cyclosporine A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289708/interruption-of-ox40l-signaling-prevents-costimulation-blockade-resistant-allograft-rejection
#7
William H Kitchens, Ying Dong, David V Mathews, Cynthia P Breeden, Elizabeth Strobert, Maria E Fuentes, Christian P Larsen, Mandy L Ford, Andrew B Adams
The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28267882/early-conversion-to-belatacept-after-renal-transplantation
#8
Vinay Nair, Luz Liriano-Ward, Rebecca Kent, Shirish Huprikar, Mena Rana, Sander S Florman, Veronica B Delaney, Madhav C Menon, Vinita Sehgal, Leandra Miko, Rafael Khaim, Alan Benvenisty, Susan Lerner, Antonios Arvelakis, Vikram Wadhera, Scott Ames, Ron Shapiro
Belatacept is a non-nephrotoxic immunosuppressive agent, which may make it the ideal agent for patients with delayed or slow graft function on calcineurin inhibitors. There are limited data on conversion of patients to belatacept within 6 months of transplantation. Between January 2012 and December 2015, 16 patients were converted to belatacept for delayed or poor graft function (eGFR<30 mL/min/1.73 m(2) , MDRD); three were HIV positive. Conversion protocols were analyzed in patients ≤4 months and 4-6 months post-transplantation...
March 7, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28166398/belatacept-after-kidney-transplantation-in-adolescents-a-retrospective-study
#9
Christian Lerch, Nele K Kanzelmeyer, Thurid Ahlenstiel-Grunow, Kerstin Froede, Martin Kreuzer, Jens Drube, Murielle Verboom, Lars Pape
Regardless of recipient age at kidney transplantation (KTx), patients are at greatest risk for graft loss in adolescence, partly due to nonadherence to an oral immunosuppressive regimen. Belatacept, a non-nephrotoxic, first-in-class immunosuppressant that inhibits costimulation of T cells requires intravenous application only every 4 weeks, potentially leading to better adherence. However, it is only approved for use in adults. We report here the findings of the first study of belatacept in adolescents, comprising all patients in our department switched to belatacept post-KTx...
February 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28104134/eculizumab-and-belatacept-for-de-novo-atypical-hemolytic-uremic-syndrome-associated-with-cfhr3-cfhr1-deletion-in-a-kidney-transplant-recipient-a-case-report
#10
P Dedhia, A Govil, G Mogilishetty, R R Alloway, E S Woodle, B G Abu Jawdeh
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway. CASE REPORT: We report a case of post-living kidney transplantation de novo aHUS in a setting of heterozygous deletion in the complement factor H-related protein (CFHR)3-CFHR1 gene. The aHUS episode was possibly triggered by antibody-mediated rejection or tacrolimus...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28078228/belatacept-in-renal-transplantation-quo-vadis
#11
COMMENT
Timm H Westhoff
No abstract text is available yet for this article.
December 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/27996207/complete-regression-of-psoriatic-arthritis-after-belatacept-conversion-in-a-highly-hla-sensitized-kidney-transplant-patient
#12
M Meneghini, C Gómez, R Mast, E Melilli, J M Grinyó, O Bestard
Costimulatory inhibitors (i.e. abatacept and belatacept) effectively abrogate T lymphocyte activation and proliferation and have been shown to be effective for disease control in certain autoimmune disorders as well as in preventing allograft rejection in kidney transplantation. Whether such immunomodulatory agents may be useful for the control of autoimmune flares and allograft acceptance, while avoiding the need of additional strong immunosuppressants, has not been shown. Here, we report the first case of a 47-year-old man affected by a serious debilitating form of psoriatic arthritis that presented during the course of a third, high immunological-risk kidney transplantation...
December 20, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27941427/belatacept-compared-to-tacrolimus-for-kidney-transplantation-a-propensity-score-matched-cohort-study
#13
Jordana B Cohen, Kevin C Eddinger, Kimberly A Forde, Peter L Abt, Deirdre Sawinski
BACKGROUND: While tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exists to directly compare outcomes with belatacept-based regimens to tacrolimus. METHODS: We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001 and December 31, 2015 using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept versus tacrolimus-based regimens...
December 8, 2016: Transplantation
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#14
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932109/risk-evaluation-and-outcome-of-pneumocystis-jirovecii-pneumonia-in-kidney-transplant-patients
#15
S Brakemeier, M Dürr, F Bachmann, D Schmidt, J Gaedeke, K Budde
Pneumocystis jirovecii pneumonia (PJP) affects immunocompromised patients. As a result of effective prophylaxis in the 1st months after kidney transplantation, PJP is increasingly diagnosed in the long term after transplantation. The present study evaluates course and outcome of PJP in a single transplant center from 2010 to 2015. Twenty-three patients presented with PJP at a mean of 53.7 ± 50.2 months after transplantation. Of these, 3 patients underwent ABO-incompatible (ABO-i) living-donor transplantation and 3 patients were treated with the use of belatacept...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27889299/safety-and-efficacy-outcomes-3-years-after-switching-to-belatacept-from-a-calcineurin-inhibitor-in-kidney-transplant-recipients-results-from-a-phase-2-randomized-trial
#16
Josep M Grinyó, Maria Del Carmen Rial, Josefina Alberu, Steven M Steinberg, Roberto C Manfro, Georgy Nainan, Flavio Vincenti, Charlotte Jones-Burton, Nassim Kamar
BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1...
May 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27888551/selective-targeting-of-high-affinity-lfa-1-does-not-augment-costimulation-blockade-in-a-nonhuman-primate-renal-transplantation-model
#17
K P Samy, D J Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer, S C Kachlany, K A Reimann, T How, F V Leopardi, K S Franke, K D Williams, B H Collins, A D Kirk
Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27881707/a-cd80-biased-ctla4-ig-fusion-protein-with-superior-in-vivo-efficacy-by-simultaneous-engineering-of-affinity-selectivity-stability-and-fcrn-binding
#18
Julie Douthwaite, Jacques Moisan, Cyril Privezentzev, Blagoje Soskic, Shereen Sabbah, Suzanne Cohen, Andie Collinson, Elizabeth England, Catherine Huntington, Ben Kemp, Li Zhuang, Suzanne Hudak, D Gareth Rees, Debbie Goldberg, Chris Barton, Linda Chang, Inna Vainshtein, Meina Liang, Laurie Iciek, Philip Ambery, Mark Peakman, Tristan J Vaughan, Tim I M Tree, David M Sansom, Michael A Bowen, Ralph R Minter, Lutz Jermutus
Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27861289/the-effect-of-asp2409-a-novel-cd86-selective-variant-of-ctla4-ig-on-renal-allograft-rejection-in-nonhuman-primates
#19
Shinsuke Oshima, Erik E Karrer, Yuka Kawato, Masashi Maeda, Hidehiko Fukahori, Susumu Tsujimoto, Jun Hirose, Koji Nakamura, Takanori Marui, Fujiko Takamura, Takahisa Noto, Steven J Chapin, Yasutomo Fujii, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi
BACKGROUND: Blockade of CD28-mediated T cell costimulation by a modified cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig), belatacept, is a clinically effective immunosuppressive therapy for the prevention of renal allograft rejection. Use of belatacept-based calcineurin inhibitor-free immunosuppression, however, has demonstrated an increased frequency of cellular rejection episodes and immunosuppression-related safety issues relative to conventional regimens. Furthermore, belatacept typically requires infusion for its administration chronically, which may present an inconvenience to patients...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27847589/belatacept-conversion-in-african-american-kidney-transplant-recipients-with-severe-renal-dysfunction
#20
Heather S Snyder, Benjamin T Duhart, Amy G Krauss, Vinaya Rao
OBJECTIVES: Conversion from calcineurin inhibitor-based maintenance immunosuppression to belatacept in kidney transplant recipients has been demonstrated to improve renal function while maintaining efficacy against rejection. However, conversion studies to date have excluded patients with an estimated glomerular filtration rate < 35 mL/min/1.73 m(2). METHODS: We describe two patients with an estimated glomerular filtration rate < 30 mL/min/1.73 m(2) who underwent conversion from maintenance calcineurin inhibitor to belatacept...
2016: SAGE open medical case reports
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