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acute rejection therapy

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https://www.readbyqxmd.com/read/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#1
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
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
#2
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...
November 23, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27888576/total-recall-can-we-reshape-t-cell-memory-by-lymphoablation
#3
Michael Nicosia, Anna Valujskikh
Despite recent advances in immunosuppression, donor-reactive memory T cells remain a serious threat to successful organ transplantation. To alleviate damaging effects of preexisting immunologic memory, lymphoablative induction therapies are used as a part of standard care in sensitized recipients. However, there is accumulating evidence that memory T cells have advantages over their naïve counterparts in surviving depletion and expanding under lymphopenic conditions. This may at least partially explain the inability of existing lymphoablative strategies to improve long term allograft outcome in sensitized recipients, despite well-documented decrease in the frequency of early acute rejection episodes...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27878210/t-regulatory-cell-mediated-immunotherapy-for-solid-organ-transplantation-a-clinical-perspective
#4
Mohammad Afzal Khan
T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection...
November 22, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27876281/post-transplant-surveillance-for-acute-rejection-and-allograft-vasculopathy-by-echocardiography-usefulness-of-myocardial-velocity-and-deformation-imaging
#5
Michael Dandel, Roland Hetzer
Diagnosing and monitoring acute rejection (AR) and cardiac allograft vasculopathy (CAV) is essential for graft and transplant patient survival and, consequently, a major objective for heart transplant patient surveillance. Because functionally relevant CAV can arise and progress without clinical symptoms and sub-clinical ARs can facilitate the development of CAV, standard surveillance of AR and CAV includes routine endomyocardial biopsy (EMB) and coronary angiography (CA) screenings at pre-defined time intervals...
October 7, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27871759/rabbit-atg-or-basiliximab-induction-for-rapid-steroid-withdrawal-after-renal-transplantation-harmony-an-open-label-multicentre-randomised-controlled-trial
#6
Oliver Thomusch, Michael Wiesener, Mirian Opgenoorth, Andreas Pascher, Rainer Peter Woitas, Oliver Witzke, Bernd Jaenigen, Markus Rentsch, Heiner Wolters, Thomas Rath, Tülay Cingöz, Urs Benck, Bernhard Banas, Christian Hugo
BACKGROUND: Standard practice for immunosuppressive therapy after renal transplantation is quadruple therapy using antibody induction, low-dose tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake significantly increases cardiovascular risk factors with negative effects on the outcome, especially post-transplantation diabetes associated with morbidity and mortality. In this trial, we examined the efficacy and safety parameters of rapid steroid withdrawal after induction therapy with either rabbit antithymocyte globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during the first year after kidney transplantation...
November 18, 2016: Lancet
https://www.readbyqxmd.com/read/27866926/evaluation-of-humoral-immunity-profiles-to-identify-heart-recipients-at-risk-for-development-of-severe-infections-a-multicenter-prospective-study
#7
Elizabeth Sarmiento, Maria Jaramillo, Leticia Calahorra, Juan Fernandez-Yañez, Miguel Gomez-Sanchez, Maria G Crespo-Leiro, Maria Paniagua, Luis Almenar, Monica Cebrian, Gregorio Rabago, Beltran Levy, Javier Segovia, Manuel Gomez-Bueno, Javier Lopez, Sonia Mirabet, Joaquin Navarro, Juan Jose Rodriguez-Molina, Eduardo Fernandez-Cruz, Javier Carbone
BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV)...
October 17, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27865034/prevention-of-hepatitis-c-recurrence-by-bridging-sofosbuvir-ribavirin-from-pre-to-post-liver-transplant-a-real-life-strategy
#8
Maria Francesca Donato, Cristina Morelli, Renato Romagnoli, Federica Invernizzi, Chiara Mazzarelli, Rosa Maria Iemmolo, Marzia Montalbano, Ilaria Lenci, Sherrie Bhoori, Giulia Pieri, Sonia Berardi, Paolo Caraceni, Silvia Martini
BACKGROUND AND AIMS: Hepatitis C virus (HCV) reinfection following liver transplant (LT) is associated with reduced graft and patients survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 week HCV-RNA undetectability at the time of transplant...
November 19, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27864897/tolerogenic-dendritic-cell-therapy-in-organ-transplantation
#9
REVIEW
Aurélie Moreau, Brigitte Alliot-Licht, Maria-Cristina Cuturi, Gilles Blancho
Although the occurrence of acute rejection was significantly reduced and the allograft survival at one year was massively improved by the development of pharmacological immunosuppressive drugs, little progress has been made regarding long-term graft survival. Cell therapy appears to be an innovative and promising strategy to minimize the use of immunosuppression in transplantation and consequently increases long-term graft survival. The strength of cell therapy is that it will induce graft-specific tolerance and not a general immunosuppression of the patients...
November 19, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27855589/twice-daily-telaprevir-for-posttransplant-genotype-1-hepatitis-c-virus-a-prospective-safety-efficacy-and-pharmacokinetics-study
#10
Raymond A Rubin, Mark W Russo, Kimberly A Brown, Robert J Fontana, Josh Levitsky, Hugo Vargas, Eric M Yoshida, Robert S Brown
OBJECTIVES: Our objective was to determine the safety, efficacy, and pharmacokinetics of telaprevir plus pegylated interferon alfa 2a and ribavirin for chronic, posttransplant genotype 1 hepatitis C virus infection. MATERIALS AND METHODS: A prospective, single-arm, multicenter, open-label, phase 2b study was conducted at 22 North American sites to assess the safety, efficacy, and pharmacokinetics of pegylated interferon alfa 2a, ribavirin, and twice daily telaprevir in liver transplant recipients with recurrent, chronic hepatitis C without cirrhosis...
November 18, 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27820833/multiparametric-functional-mri-a-tool-to-uncover-subtle-changes-following-allogeneic-renal-transplantation
#11
Mike Notohamiprodjo, Aivars Kalnins, Martin Andrassy, Manuel Kolb, Benjamin Ehle, Susanna Mueller, Michael N Thomas, Jens Werner, Markus Guba, Konstantin Nikolaou, Joachim Andrassy
PURPOSE: To investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics. MATERIAL AND METHODS: We performed allogeneic and syngeneic orthotopic transplantations (Balb/c to C57Bl/6 and C57Bl/6 to C57Bl/6). Allogeneic Groups (n = 5) were either treated with the anti-CCL2-Spiegelmer (mNOX-E36) in monotherapy or in combination with low doses of Ciclosporin-A (10mg/kgBW/d) for 10 days...
2016: PloS One
https://www.readbyqxmd.com/read/27813419/anti-interleukin-2-receptor-antibodies-for-the-prevention-of-rejection-in-liver-transplant-recipients-a-systematic-review-and-meta-analysis
#12
Yi Zhang, Weidong Jin, Xun Cai
BACKGROUND: Antibody induction therapy aims to prevent acute cellular rejection by reducing T-cell proliferation and activation. We evaluated the efficacy and side effects of two anti-interleukin-2 receptor antibodies (IL2RA), basiliximab and daclizumab, for prevention of liver transplant rejection in adult patients. METHODS: Randomized controlled trials on basiliximab or daclizumab were identified by searching multiple databases and reference lists published up to July, 2015...
November 4, 2016: Annals of Medicine
https://www.readbyqxmd.com/read/27812112/systematic-review-and-meta-analysis-of-tacrolimus-versus-ciclosporin-as-primary-immunosuppression-after-liver-transplant
#13
Gorden Muduma, Rhodri Saunders, Isaac Odeyemi, Richard F Pollock
BACKGROUND AND AIMS: Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs) predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000...
2016: PloS One
https://www.readbyqxmd.com/read/27798373/prolongation-of-cardiac-allograft-survival-by-endometrial-regenerative-cells-focusing-on-b-cell-responses
#14
Xiaoxi Xu, Xiaochun Li, Xiangying Gu, Bai Zhang, Weijun Tian, Hongqiu Han, Peng Sun, Caigan Du, Hao Wang
: : Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2(b)) donor mice and BALB/c (H-2(d)) recipients...
October 26, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27798202/anti-thymocyte-globulins-in-kidney-transplantation-focus-on-current-indications-and-long-term-immunological-side-effects
#15
REVIEW
Jamal Bamoulid, Oliver Staeck, Thomas Crépin, Fabian Halleck, Philippe Saas, Susanne Brakemeier, Didier Ducloux, Klemens Budde
Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug...
October 25, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27797067/spontaneous-resolution-of-de-novo-hepatitis-b-after-living-donor-liver-transplantation-with-hepatitis-b-core-antibody-positive-graft-a-case-report
#16
Yasuyuki Hara, Kazuaki Tokodai, Chikashi Nakanishi, Shigehito Miyagi, Naoki Kawagishi
BACKGROUND: Hepatitis B core antibody (HBcAb)-positive graft is reported to cause de novo hepatitis B after liver transplantation with a probability of 38-100 % without prophylaxis. Hepatitis B surface antigen loss is reported to be achieved with a probability of only 3-8 % in the patients treated by antiviral agents. We present an extremely rare case of spontaneous resolution of de novo hepatitis B after living donor liver transplantation (LDLT) with HBcAb-positive graft. CASE PRESENTATION: An 8-year-old female patient underwent LDLT for end-stage biliary atresia using an HBcAb-positive left lobe graft...
December 2016: Surgical Case Reports
https://www.readbyqxmd.com/read/27795990/early-kidney-allograft-dysfunction-threatened-allograft-comparative-effectiveness-of-continuing-versus-discontinuation-of-tacrolimus-and-use-of-sirolimus-to-prevent-graft-failure-a-retrospective-patient-centered-outcome-study
#17
Ravinder K Wali, Heather A Prentice, Venkata Reddivari, Geroge Baffoe-Bonnie, Cinthia I Drachenberg, John C Pappadimitriou, Emilio Ramos, Matthew Cooper, Johann Jonsson, Stephen Bartlett, Matthew R Weir
BACKGROUND: Due to lack of treatment options for early acute allograft dysfunction in the presence of tubular-interstitial injury without histological features of rejection, kidney transplant recipients are often treated with sirolimus-based therapy to prevent cumulative calcineurin inhibitor exposure and to prevent premature graft failure. METHODS: We analyzed transplant recipients treated with sirolimus-based (n = 220) compared with continued tacrolimus-based (n = 276) immunosuppression in recipients of early-onset graft dysfunction (threatened allograft) with the use of propensity score-based inverse probability treatment weighted models to balance for potential confounding by indication between 2 nonrandomized groups...
September 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27795623/rituximab-in-the-treatment-of-refractory-late-acute-antibody-mediated-rejection-our-initial-experience
#18
M Surendra, S B Raju, N Raju, S Chandragiri, K K Mukku, M S Uppin
Antibody-mediated rejection (AMR) is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m(2). The mean age of patients was 35.3 ± 7...
September 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27788796/surveillance-registry-of-sirolimus-use-in-recipients-of-kidney-allografts-from-expanded-criteria-donors
#19
G Laham, R Scuteri, P Cornicelli, M Arriola, P M Raffaele, M Davalos Michel, N Imperiali, R M Fortunato, E C Maggiora, M V Sal, G Soler Pujol
BACKGROUND: The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys. METHODS: This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27788794/impact-of-trough-levels-of-tacrolimus-on-kidney-function-and-graft-survival-in-short-and-longer-periods-after-renal-transplantation
#20
Z Žilinská, I Dedinská, J Breza, L Laca
BACKGROUND: Optimizing immunosuppressive treatment in the early posttransplant period is important for achieving long-term graft function and survival. MATERIAL AND METHODS: There were 205 renal transplant recipients involved in this study. Patients were divided into groups according to the induction therapy (no induction vs basiliximab/daclizumab vs rabbit antithymocyte globulin), maintenance therapy at the time of transplantation (tacrolimus [TAC] vs cyclosporine), the average trough TAC levels in months 4 to 6 after TO and serum creatinine 5 years after renal transplantation...
October 2016: Transplantation Proceedings
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