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Antibody rejection

William H Marks, Nizam Mamode, Robert Montgomery, Mark D Stegall, Lloyd E Ratner, Lynn D Cornell, Ajda T Rowshani, Robert B Colvin, Bradley Dain, Judith A Boice, Denis Glotz
We report results of a phase 2, randomized, multicenter, open-label, two-arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in sensitized recipients of living-donor kidney transplants requiring pretransplantation desensitization (NCT01399593). In total, 102 patients underwent desensitization. Posttransplantation, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplantation treatment failure rate, a composite of: biopsy-proven acute AMR (Banff 2007 grades II or III; assessed by blinded central pathology); graft loss; death; or loss to follow-up...
March 19, 2019: American Journal of Transplantation
Jeff Reeve, Georg A Böhmig, Farsad Eskandary, Gunilla Einecke, Gaurav Gupta, Katelynn Madill-Thomsen, Martina Mackova, Philip F Halloran
We previously reported a system for assessing rejection in kidney transplant biopsies using microarray-based gene expression data, the Molecular Microscope® Diagnostic System (MMDx). The present study was designed to optimize the accuracy and stability of MMDx diagnoses by replacing single machine learning classifiers with ensembles of diverse classifier methods. We also examined the use of automated report sign-outs and the agreement between multiple human interpreters of the molecular results. Ensembles generated diagnoses that were both more accurate than the best individual classifiers, and nearly as stable as the best, consistent with expectations from the machine learning literature...
March 13, 2019: American Journal of Transplantation
Hyunwook Kwon, Young Hoon Kim, Jee Yeon Kim, Ji Yoon Choi, Sung Shin, Joo Hee Jung, Su-Kil Park, Duck Jong Han
BACKGROUND: Crossmatching (XM) between organ donors and recipients is correlated with clinical outcomes. This study evaluates the results of HLA-incompatible kidney transplant (HLA-i KT) according to pre-transplant XM modalities. METHODS: This study included 731 consecutive patients. HLA-i KT was defined as a transplant under conditions of complement-dependent cytotoxicity (CDC) XM positivity, flow-cytometric XM (FCXM) positivity, and/or maximal donor-specific antibody (DSA) mean fluorescence intensity (MFI) ≥5000...
March 12, 2019: Clinical Transplantation
Brett Rollins, Samira Farouk, Graciela DeBoccardo, Susan Lerner, Meenakshi Rana, Shirish Huprikar, Leandra Miko, Veronica Delaney, Sander Florman, Ron Shapiro
Rejection rates in HIV-infected kidney transplant (KTx) recipients are higher than HIV-negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug-drug interactions, likely influencing outcomes. This is an IRB-approved, single-center, retrospective study of adult HIV infected KTx patients between 5/2009-12/2014 with three-year follow-up, excluding antibody-depleting induction. 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian...
March 12, 2019: Clinical Transplantation
Mohammad Yazdani, Nasser Ghaemian, Soraya Khafri, Farshid Oliaei
Background: The aim of this study was to use the volume of the graft as an adjunct tool for better decision making. Methods: Kidney transplanted patients with acute azotemia and documented volume and finally a biopsy were enrolled in this study‌. Graft volumes between rejected patients (antibody-mediated rejection {AMR} and cell - mediated rejection {CMR}) and ‌non rejected but azotemic patients were compared. Results: A total of 76 patients were enrolled in this study ‌(45 case and 31 control‌)...
2019: Caspian Journal of Internal Medicine
Xinyu Li, Qiang Meng, Lei Zhang
Porcine islets might represent an ideal solution to the severe shortage of living donor islets available for transplantation and thus have great potential for the treatment of diabetes. Although tremendous progress has been achieved through recent experiments, the immune response remains a major obstacle. This review first describes the 3 major pathways of rejection: hyperacute rejection mediated by preformed natural antibodies and complement, instant blood-mediated inflammatory reactions, and acute cell-mediated rejection...
March 2019: Pancreas
Verena Broecker, Victoria Bardsley, Nicholas Torpey, Ranmith Perera, Rosa Montero, Anthony Dorling, Andrew Bentall, Desley Neil, Michelle Willicombe, Miriam Berry, Candice Roufosse
AIMS: Post-transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uremic syndrome (aHUS), TMA in renal transplants is associated with various conditions, such as calcineurin-inhibitor (CNI) treatment, antibody-mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies or surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post-transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multi-centre retrospective study...
March 9, 2019: Histopathology
Abid Aljabri, Vijith Vijayan, Metodi Stankov, Christoph Nikolin, Constanca Figueiredo, Rainer Blasczyk, Jan Ulrich Becker, Andreas Linkermann, Stephan Immenschuh
Antibody-mediated rejection (AMR) is the major cause of allograft loss after solid organ transplantation. Circulating donor-specific antibodies against human leukocyte antigen (HLA), in particular HLA class II antibodies are critical for the pathogenesis of AMR via interactions with endothelial cells (ECs). To investigate the effects of HLA class II antibody ligation to the graft endothelium, a model of HLA-DR antibody-dependent stimulation was utilized in primary human ECs. Antibody ligation of HLA class II molecules in interferon-γ-treated ECs caused necrotic cell death without complement via a pathway that was independent of apoptosis and necroptosis...
March 8, 2019: Cell Death & Disease
Marianne Delville, Baptiste Lamarthée, Sylvain Pagie, Sarah B See, Marion Rabant, Carole Burger, Philippe Gatault, Magali Giral, Olivier Thaunat, Nadia Arzouk, Alexandre Hertig, Marc Hazzan, Marie Matignon, Christophe Mariat, Sophie Caillard, Nassim Kamar, Johnny Sayegh, Pierre-François Westeel, Cyril Garrouste, Marc Ladrière, Vincent Vuiblet, Joseph Rivalan, Pierre Merville, Dominique Bertrand, Alain Le Moine, Jean Paul Duong Van Huyen, Anne Cesbron, Nicolas Cagnard, Olivier Alibeu, Simon C Satchell, Christophe Legendre, Emmanuel Zorn, Jean-Luc Taupin, Béatrice Charreau, Dany Anglicheau
BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed. METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR)...
March 8, 2019: Journal of the American Society of Nephrology: JASN
Surumi Shajahan, Sreedurga Thottanchery Sasidharan, Sudhindran Surendran, Veena Shenoy, Uma Devi Padma
BACKGROUND: Although, ABO-incompatible (ABOi) liver transplantation is considered a high-risk procedure, using newer and more effective preoperative B cell desensitisation techniques, many transplant centres are routinely performing ABOi living donor liver transplantation (LDLT). METHODS: This was a retrospective study of 12 patients (adult:pediatric = 10:2; M:F = 9:3; median age, 45.5 years [range 1 to 56 years]) who underwent ABOi LDLT at a tertiary care centre...
March 8, 2019: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Peter Vink, Josep Maria Ramon Torrell, Ana Sanchez Fructuoso, Sung-Joo Kim, Sang-Il Kim, Jeff Zaltzman, Fernanda Ortiz, Josep Maria Campistol Plana, Ana Maria Fernandez Rodriguez, Henar Rebollo Rodrigo, Magda Campins Marti, Rafael Perez, Francisco Manuel González Roncero, Deepali Kumar, Yang-Jen Chiang, Karen Doucette, Lissa Pipeleers, Maria Luisa Agüera Morales, Maria Luisa Rodriguez-Ferrero, Antonio Secchi, Shelly A McNeil, Laura Campora, Emmanuel Di Paolo, Mohamed El Idrissi, Marta López-Fauqued, Bruno Salaun, Thomas Heineman, Lidia Oostvogels
BACKGROUND: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. METHODS: In this phase III, randomized (1:1), observer-blind, multicenter trial (NCT02058589), RT recipients were enrolled and received 2 doses of RZV or Placebo 1-2 months (M) apart 4-18M post-transplant...
March 7, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Rita R Alloway, E Steve Woodle, Daniel Abramowicz, Dorry L Segev, Remi Castan, Jillian N Ilsley, Kari Jeschke, K Troy Somerville, Daniel C Brennan
This report describes the results of two international randomized trials (total of 508 kidney transplant recipients). The primary objective was to assess the noninferiority of rabbit anti-thymocyte globulin (rATG, Thymoglobulin® ) vs interleukin-2 receptor antagonists (IL2RAs) for the quadruple endpoint (treatment failure defined as biopsy-proven acute rejection, graft loss, death, or loss to follow-up) to serve as the pivotal data for US regulatory approval of rATG. The pooled analysis provided an incidence of treatment failure of 25...
March 5, 2019: American Journal of Transplantation
Kevin Louis, Alexandre Hertig, Jean-Luc Taupin, David Buob, Matthieu Jamme, Isabelle Brocheriou, Yosu Luque, Chantal Jouanneau, Nacera Ouali, Marie Audouin, Eric Rondeau, Yi-Chun Xu-Dubois
Graft microvasculature is a major target of donor-specific antibodies (DSA) and endothelial damage is a direct evidence of antibody-mediated rejection (ABMR). Using immunohistochemistry, we analyzed the expression of three microvascular endothelial activation markers (fascin, vimentin and hsp47), suggestive of endothelial-to-mesenchymal transition (EndMT) in 351 graft biopsies from 248 kidney recipients, with concomitant screening of circulating anti-human leukocyte antigen (HLA)DSA at the time of the biopsy...
March 5, 2019: American Journal of Transplantation
Christina L Kaufman, Marilia Cascalho, Tuna Ozyurekoglu, Christopher M Jones, Allan Ramirez, Tiffany Roberts, Huey Y Tien, Rodrigo Moreno, Elkin Galvis, Tsu-Min Tsai, Michelle Palazzo, Scott Farner, Jeffery Platt
Vascularized composite allotransplantation (VCA) has emerged as the most recent field of transplantation to offer an alternative treatment for those patients that have failed or are not suitable candidates for conventional therapy. Most of the current clinical experience in this field is with recipients of skin containing grafts such as the face, upper extremity and abdominal wall transplants. Like solid organ recipients, VCA recipients require lifelong systematic immunosuppression to maintain their grafts...
March 2, 2019: Human Immunology
Kiran K Khush, Jignesh Patel, Sean Pinney, Andrew Kao, Rami Alharethi, Eugene DePasquale, Gregory Ewald, Peter Berman, Manreet Kanwar, David Hiller, James P Yee, Robert N Woodward, Shelley Hall, Jon Kobashigawa
Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers, and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR)...
March 5, 2019: American Journal of Transplantation
Joseph Ladowski, Greg Martens, Jose Estrada, Matthew Tector, Joseph Tector
The humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR-Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies...
March 2, 2019: Xenotransplantation
S C Kim, D V Mathews, C P Breeden, L B Higginbotham, J Ladowski, G Martens, A Stephenson, A B Farris, E A Strobert, J Jenkins, E M Walters, C P Larsen, M Tector, A J Tector, A B Adams
The shortage of available organs remains the greatest barrier to expanding access to transplantation. Despite advances in genetic editing and immunosuppression, survival in experimental models of kidney xenotransplantation has generally been limited to <100 days. We found that pre-transplant selection of recipients with low titers of anti-pig antibodies significantly improved survival in a pig to rhesus macaque kidney transplant model (6 days vs MST 235 days). Immunosuppression included transient pan-T cell depletion and an anti-CD154-based maintenance regimen...
March 1, 2019: American Journal of Transplantation
H Xiao, X W Zhu, X G Chen, Y Yang, G F Dou, W W Wang, X X Niu, S Qiu, C F Li, Y J Niu
Objective: To investigate the correlation between the proportion of CTL and Th1 cells in peripheral blood of liver transplant recipients and the success of hepatitis B vaccination. Methods: The subjects of this study were liver transplantation recipients with chronic HBV-related liver diseases in Organ transplantation institute of the third medical center of PLA general hospital. Subjects were randomly divided into two groups for prospective study. In the rapid group, one dose of 40 μg hepatitis B vaccine was administered at 0, 1, 2and 3 months, and one dose of 20 μg hepatitis B vaccine was administered at 4, 5 and 6 months...
February 26, 2019: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Erik Berglund, Mette Andersen Ljungdahl, Darko Bogdanović, David Berglund, Jonas Wadström, Jan Kowalski, Gerald Brandacher, Dorota Kamińska, Christina L Kaufman, Simon G Talbot, Kodi Azari, Luis Landin, Christoph Höhnke, Karen M Dwyer, Pedro C Cavadas, Alessandro Thione, Brendan Clarke, Simon Kay, Dan Wilks, Subramania Iyer, Martin Iglesias, Ömer Özkan, Özlenen Özkan, Johanna Krapf, Annemarie Weissenbacher, Palmina Petruzzo, Stefan Schneeberger
BACKGROUND: Donor-specific antibodies (DSA) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. METHODS: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome...
February 22, 2019: Transplantation
Sebastian Dolff, Benjamin Wilde, Bastian Tebbe
No abstract text is available yet for this article.
February 25, 2019: Transplantation
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