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Antibody mediated rejection

Antoine Roux, Kimberly A Thomas, Edouard Sage, Caroline Suberbielle-Boissel, Laurence Beaumont-Azuar, Francois Parquin, Morgan Le Guen, Nicholas Harre, Abdul Monem Hamid, Elaine F Reed
Complement-mediated allograft injury, elicited by donor specific HLA antibodies (DSA), is a defining pathophysiological characteristic of allograft damage. We aimed to study DSA-induced complement activation as a diagnostic marker of antibody mediated rejection (AMR) and a risk stratification tool for graft loss in the context of lung transplantation (LT). We identified 38 DSA positive patients whose serum samples were submitted for C3d deposition testing via the C3d assay. Among these 38 patients, 15 had AMR (DSAP os AMRP os )...
March 14, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
Clive M Michelo, Bram van Cranenbroek, Peran Touw, Frans H J Claas, Arnold van der Meer, Irma Joosten
Background: Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity. Methods: We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells...
December 2017: Transplantation Direct
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
Carla C Baan
Developments in organ preservation techniques, novel immunosuppressants and improved diagnostics have made organ transplantation the success it is today. That does not mean that we are not still striving to perfect techniques, or that there are no more problems to solve. New strategies to address the donor organ shortage, prevent and manage antibody-mediated rejection, lower long-term allograft failure rates and reduce the toxicity of life-long immunosuppressive medication are urgently needed, and are being widely researched...
March 9, 2018: Transplantation
Redondo-Pachón Dolores, Pérez-Sáez María José, Mir Marisa, Gimeno Javier, Llinás Laura, García Carmen, Hernández Juan José, Yélamos Jose, Pascual Julio, Crespo Marta
Preformed HLA donor-specific antibodies (DSA) only detected with Luminex have been associated with increased risk of antibody-mediated rejection (ABMR) and graft failure after kidney transplantation (KT). Their evolution after KT may modify this risk. We analyzed postransplant evolution of preformed DSA identified retrospectively and their impact on outcomes of 370 KT performed 2006-2014. Antibodies were monitored prospectively at 1-3-5 years after KT and if any dysfunction. Early acute ABMR was more frequent among patients with preformed DSA class-I or I+II than isolated class-II (29...
March 7, 2018: Human Immunology
Yannick D Muller, John-David Aubert, Julien Vionnet, Samuel Rotman, Salima Sadallah, Vincent Aubert, Manuel Pascual
No abstract text is available yet for this article.
March 8, 2018: Transplantation
Takanori Marui, Hidehiko Fukahori, Tomoko Kawashima, Misato Ito, Masahiko Akamatsu, Yoko Kaneko, Fumie Takahashi, Sunao Imada, Tatsuaki Morokata
B cell-mediated antibodies play a critical role in protecting the body from infections; however, excessive antibody production is involved in the pathogenesis of autoimmune diseases and transplanted organ rejection. Regulation of antibody production is therefore crucial for overcoming these complications. Phosphatidylinositol-3-kinase p110δ (PI3Kδ), a member of the family of PI3K lipid kinases, is a key mediator of B cell activation and proliferation, with a small molecule PI3Kδ inhibitor having been approved for the treatment of B cell lymphoma...
March 5, 2018: European Journal of Pharmacology
Chien-Chia Chen, Alice Koenig, Carole Saison, Suzan Dahdal, Guillaume Rigault, Thomas Barba, Morgan Taillardet, Dimitri Chartoire, Michel Ovize, Emmanuel Morelon, Thierry Defrance, Olivier Thaunat
Antibody-mediated rejection is currently the leading cause of transplant failure. Prevailing dogma predicts that B cells differentiate into anti-donor-specific antibody (DSA)-producing plasma cells only with the help of CD4+ T cells. Yet, previous studies have shown that dependence on helper T cells decreases when high amounts of protein antigen are recruited to the spleen, two conditions potentially met by organ transplantation. This could explain why a significant proportion of transplant recipients develop DSA despite therapeutic immunosuppression...
2018: Frontiers in Immunology
R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen
Donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection and graft failure. In BENEFIT and BENEFIT-EXT, kidney transplant recipients were randomized to receive belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression for up to 7 years (84 months). The presence/absence of HLA-specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid-phase flow cytometry screening...
March 6, 2018: American Journal of Transplantation
Olivier Désy, Stéphanie Béland, Patrice Vallin, Julie Riopel, Eva Latulippe, Eric Wagner, Sacha A De Serres
Follicular helper T cells (Tfh) are crucial for the production of high-affinity antibodies, such as alloantibodies, by providing the signals for B-cell proliferation and differentiation. Here, we demonstrate that human allogeneic dendritic cells (DC) stimulated with antibodies against HLA class II antigens preferentially differentiate human naive CD4+ T cells into Tfh cells. Following coculture with DCs treated with these antibodies, CD4+ T cells expressed CXCR5, ICOS, IL-21, Bcl-6 and phosphorylated STAT3...
March 5, 2018: Scientific Reports
Sean Agbor-Enoh, Annette M Jackson, Ilker Tunc, Gerald J Berry, Adam Cochrane, David Grimm, Andrew Davis, Pali Shah, Anne W Brown, Yan Wang, Irina Timofte, Palak Shah, Sasha Gorham, Jennifer Wylie, Natalie Goodwin, Moon Kyoo Jang, Argit Marishta, Kenneth Bhatti, Ulgen Fideli, Yanqin Yang, Helen Luikart, Zeling Cao, Mehdi Pirooznia, Jun Zhu, Charles Marboe, Aldo Iacono, Steven D Nathan, Jonathan Orens, Hannah A Valantine, Kiran Khush
BACKGROUND: Antibody-mediated rejection (AMR) often progresses to poor health outcomes in lung transplant recipients (LTRs). This, combined with the relatively insensitive clinical tools used for its diagnosis (spirometry, histopathology) led us to determine whether clinical AMR is diagnosed significantly later than its pathologic onset. In this study, we leveraged the high sensitivity of donor-derived cell-free DNA (ddcfDNA), a novel genomic tool, to detect early graft injury after lung transplantation...
January 31, 2018: Journal of Heart and Lung Transplantation
Anne I Dipchand
Pediatric heart transplantation is standard of care for children with end-stage heart failure. The diverse age range, diagnoses, and practice variations continue to challenge the development of evidence-based practices and new technologies. Outcomes in the most recent era are excellent, especially with the more widespread use of ventricular assist devices (VADs). Waitlist mortality remains high and knowledge of risk factors for death while waiting and following transplantation contributes to decision-making around transplant candidacy and timing of listing...
January 2018: Annals of Cardiothoracic Surgery
Jing-Hung Wang, Alexis V Forterre, Jingjing Zhao, Daniel O Frimannsson, Alain Delcayre, Travis J Antes, Bradley Efron, Stefanie S Jeffrey, Mark D Pegram, A C Matin
This paper deals with specific targeting of the prodrug/enzyme regimen, CNOB/HChrR6, to treat a serious disease namely HER2+ve human breast cancer with minimal off-target toxicity. HChrR6 is an improved bacterial enzyme that converts CNOB into the cytotoxic drug MCHB. Extracellular vesicles (EVs) were used for mRNA-based HchrR6 gene delivery: EVs may cause minimal immune rejection, and mRNA may be superior to DNA for gene delivery. To confine HChrR6 generation and CNOB activation to the cancer, the EVHB chimeric protein was constructed...
February 26, 2018: Molecular Cancer Therapeutics
Martin Andreas, Kathrin Freystaetter, Martin H Bernardi, Andreas Zuckermann
A 31-year-old male patient underwent a heart transplantation due to dilated cardiomyopathy. He experienced accelerated acute antibody-mediated rejection despite being negative for human leukocyte antigen antibodies (0% panel-reactive antibodies prior to surgery). Further assessment revealed a common antigen between a homograft implanted 17 years earlier during the Ross procedure and the heart donor. The homograft likely induced specific antibody formation. Interestingly, panel-reactive antibody levels measured 7 years prior to transplantation were 7%...
February 21, 2018: European Journal of Cardio-thoracic Surgery
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
M L Arnold, A Kainz, L G Hidalgo, F Eskandary, N Kozakowski, M Wahrmann, H Haslacher, R Oberbauer, A Heilos, B M Spriewald, P F Halloran, G A Böhmig
Fc-dependent effector mechanisms may contribute to antibody-mediated rejection (ABMR), and distinct gene polymorphisms modifying the function of Fc gamma receptors (FcγR) may potentially influence the capability of donor-specific antibodies (DSA) to trigger inflammation. To evaluate the relevance of functional FcγR variants in late ABMR, 85 DSA-positive kidney allograft recipients, who were recruited upon antibody screening of 741 prevalent patients, were genotyped for polymorphisms in FcγRIIA (FCGR2A-H/R131 ; rs1801274), FcγRIIIA (FCGR3A-V/F158 ; rs396991) and FcγRIIIB [FCGR3B-neutrophil antigen 1 (NA1)/NA2; rs35139848]...
February 25, 2018: American Journal of Transplantation
David K C Cooper, H Iwase, L Wang, T Yamamoto, Qi Li, J Li, H Zhou, H Hara
BACKGROUND: There is a continuing critical shortage of organs from deceased human donors for transplantation, particularly for patients awaiting kidney transplantation. Efforts are being made to resolve the donor kidney shortage by the transplantation of kidneys from genetically-engineered pigs. SUMMARY: This review outlines the pathobiological barriers to pig organ xenotransplantation in primates, which include (i) antibody-dependent complement-mediated rejection, (ii) a T cell-mediated elicited antibody and cellular response, (iii) coagulation dysregulation between pigs and primates, and (iv) a persistent inflammatory response...
January 26, 2018: Blood Purification
Yi-Ping Jin, Nicole M Valenzuela, Xiaohai Zhang, Enrique Rozengurt, Elaine F Reed
Transplant recipients developing donor-specific HLA class II (HLA-II) Abs are at higher risk for Ab-mediated rejection (AMR) and transplant vasculopathy. To understand how HLA-II Abs cause AMR and transplant vasculopathy, we determined the signaling events triggered in vascular endothelial cells (EC) following Ab ligation of HLA-II molecules. HLA-II expression in EC was induced by adenoviral vector expression of CIITA or by pretreatment with TNF-α/IFN-γ. Ab ligation of class II stimulated EC proliferation and migration...
February 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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