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Chronic antibody rejection

Sandesh Parajuli, Didier A Mandelbrot, Brenda Muth, Maha Mohamed, Neetika Garg, Fahad Aziz, Robert R Redfield, Weixiong Zhong, Brad C Astor, Arjang Djamali
Background: There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation. Methods: In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks...
December 2017: Transplantation Direct
Shokoufeh Savaj, Seyedeh Ghazal Hosseini, Ahad J Ghods
INTRODUCTION: Non-human leukocyte antigen antibodies are an independent risk factor for acute rejection in kidney transplant recipients. Among them, angiotensin II receptor type 1 (ART1) antibodies can induce various effects, but their clinical importance in kidney transplant recipients has not been properly explained. This study aimed to evaluate the effect of ART1 antibodies on allograft function and hypertension in stable kidney transplant recipients. MATERIALS AND METHODS: Eighty-one kidney recipients from non- human leukocyte antigen antibodies-matched donors with stable allograft function were examined for estimated glomerular filtration rate (Chronic Kidney Disease-Epidemiology Collaboration formula) and ART1 antibodies (measured using an enzyme-linked immunosorbent assay method)...
March 2018: Iranian Journal of Kidney Diseases
Guosheng Wu, Ruy J Cruz
Background and aims: A co-transplanted liver allograft has been thought to protect other organs from rejection-mediated injury; however, detailed analyses of co-transplanted liver on intestinal allograft outcomes have not been conducted to date. The aim of the study was to compare immune-mediated injury, causes of graft failure and clinical outcomes between recipients who underwent either a liver-inclusive intestinal transplant (LITx) or liver-exclusive intestinal transplant (LETx). Methods: Between May 2000 and May 2010, 212 adult patients undergoing LITx ( n  =76) and LETx ( n  =136) were included...
February 2018: Gastroenterology Report
Roberta Angelico, Undine A Gerlach, Bridget K Gunson, Desley Neil, Hynek Mergental, John Isaac, Paolo Muiesan, Darius Mirza, M Thamara Pr Perera
BACKGROUND: Causes of severe cholestasis following liver transplantation(LT) are multi-factorial; whilst the aetiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge. METHODS: This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90-days of LT...
February 20, 2018: Transplantation
Ergun Velidedeoglu, Marc W Cavaillé-Coll, Shukal Bala, Ozlem A Belen, Yan Wang, Renata Albrecht
BACKGROUND: Despite major advances in understanding the pathophysiology of antibody mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T-cell mediated rejection (TCMR), de novo donor specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. METHODS: On April 12-13, 2017, the Food and Drug Administration (FDA) sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in GFR, and challenges of clinical trial design for the prevention and treatment of AMR...
February 20, 2018: Transplantation
H L Stevenson, M M Prats, K Isse, A Zeevi, Y Avitzur, V L Ng, A J Demetris
According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with co-existent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified 9 patients at a mean of 1,805 days post-transplantation and compared these to matched controls...
February 21, 2018: American Journal of Transplantation
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
The article "Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation", written by Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom.
February 8, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Michael Kaabak, Nadeen Babenko, Ron Shapiro, Allan Zokoyev, Olga Dymova, Edward Kim
Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016...
January 29, 2018: Pediatric Transplantation
Marjorie-Anne R Guerra, Bita V Naini, Jason V Scapa, Elaine F Reed, Ronald W Busuttil, Elaine Y Cheng, Douglas G Farmer, Jorge H Vargas, Robert S Venick, Sue V McDiarmid, Laura J Wozniak
The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV...
January 24, 2018: Pediatric Transplantation
Juan C Ramirez-Sandoval, Ricardo Varela-Jimenez, Luis E Morales-Buenrostro
We report a case of capillary leak that developed during treatment of antibody-mediated rejection in a kidney transplant recipient. A 53-year-old female transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8 mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated with five plasmapheresis sessions (on alternate days with albumin replacement), five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab (500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1...
January 17, 2018: CEN Case Reports
Sophie De Seigneux, Belen Ponte, Karine Hadaya, Yassine Bouatou, Patrick Saudan
New antidiabetic drugs which slow effectively the course of diabetic nephropathy are now available. There is no benefit of prophylactic hydratation to prevent contrast nephropathy in patients with moderate chronic kidney disease. In elderly hemodialysis patients, hemodiafiltration seems better tolerated than conventional hemodialysis, although there is a similar dialysis-induced myocardial stress with both methods. Role of de novo donor-specific antibodies is better characterized, which may subsequently lead to new treatments of graft rejection...
January 10, 2018: Revue Médicale Suisse
Augusto Lauro, Mihai Oltean, Ignazio R Marino
Chronic rejection affects the long-term survival of all solid organ transplants and, among intestinal allografts, occurs in up to 10% of the recipients. The insidious clinical evolution of the chronic allograft enteropathy, the absence of noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No pharmacological approach has been proven effective, and allograft removal nowadays still represents the only available therapy. The inclusion of the liver in the visceral allograft appears to be the only intervention affecting the development of chronic rejection, as revealed by large-center studies and registry reports...
January 11, 2018: Digestive Diseases and Sciences
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
Mark Benzimra, Greg L Calligaro, Allan R Glanville
Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation...
December 2017: Journal of Thoracic Disease
Yoshito Yamada, Tim Langner, Ilhan Inci, Christian Benden, Macé Schuurmans, Walter Weder, Wolfgang Jungraithmayr
OBJECTIVES: Human leucocyte antigen (HLA) mismatch between donor and recipient has a differential impact on the outcome after transplant (Tx) among transplantable solid organs. Although the lung is considered a highly antigenic organ, the impact of HLA matching between the donor and the recipient has been shown to be heterogeneous on lung Tx outcome. To provide further evidence that HLA matching should be considered in the decision process prior to lung Tx, we evaluated the impact of donor/recipient HLA mismatch on the outcome after lung Tx at our institution...
January 2, 2018: Interactive Cardiovascular and Thoracic Surgery
Mark Haas
PURPOSE OF REVIEW: To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. RECENT FINDINGS: The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR...
January 2, 2018: Current Opinion in Nephrology and Hypertension
R N Smith, M Matsunami, B A Adam, I A Rosales, T Oura, A B Cosimi, T Kawai, M Mengel, R B Colvin
Tolerance induction to prevent allograft rejection is a long standing clinical goal. However, convincing and dependable tolerance identification remains elusive. Hypothesizing that intragraft RNA expression is informative in both rejection and tolerance, we profile intra-renal allograft RNA expression in a mixed chimerism renal allograft model of Cynomolgus monkeys and identify biologically significant tolerance. Analysis of 67 genes identified three dominant factors, each with a different pattern of gene expressions, relating to T cell mediated rejection (TCMR), chronic antibody mediated rejection (CAMR), or Tolerance...
December 29, 2017: American Journal of Transplantation
R N Smith, B A Adam, I A Rosales, M Matsunami, T Oura, A B Cosimi, T Kawai, M Mengel, R B Colvin
RNA transcript expression estimates are a promising method to study the mechanisms and classification of renal allograft rejections. Here we use the Nanostring platform to profile RNA expression in renal allografts in a nonhuman primate (NHP), the Cynomolgus monkey. We analyzed protocol and indication 278 archival renal allograft samples, both protocol and indication from 76 animals with diagnoses of chronic antibody-mediated rejection (CAMR), acute cellular rejection (TCMR), and MIXED (both CAMR and TCMR), plus normals and samples with no pathological rejection using a Cynomolgus-specific probe set of 67 genes...
December 29, 2017: American Journal of Transplantation
Louisa Kühne, Bettina Jung, Helen Poth, Antonia Schuster, Simone Wurm, Petra Ruemmele, Bernhard Banas, Tobias Bergler
BACKGROUND: Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A. In analogy to non-adherence to therapy, one group received cyclosporine A on alternating days only...
December 19, 2017: BMC Immunology
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