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Antibody mediated rejection

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https://www.readbyqxmd.com/read/28453891/towards-a-better-risk-stratification-for-late-antibody-mediated-rejection-in-abo-incompatible-kidney-recipients
#1
Philippe Grimbert
During the last 25 years, increasing organ shortage enforced the development for living donor programs including ABO-incompatible (ABOi) renal transplantation, paired donor exchange program and transplantation across a positive cross-match. ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantation. This article is protected by copyright. All rights reserved.
April 28, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28449409/real-time-central-assessment-of-kidney-transplant-indication-biopsies-by-microarrays-the-intercomex-study
#2
Philip F Halloran, Jeff Reeve, Enver Akalin, Olivier Aubert, Georg A Bohmig, Daniel Brennan, Jonathan Bromberg, Gunilla Einecke, Farsad Eskandary, Clement Gosset, Jean-Paul Duong Van Huyen, Gaurav Gupta, Carmen Lefaucheur, Andrew Malone, Roslyn B Mannon, Daniel Seron, Joana Sellares, Matthew Weir, Alexandre Loupy
We performed a prospective trial to assess the feasibility of real-time central molecular assessment of kidney transplant biopsies from 10 North American and European centers. Biopsies taken one day to 34 years post-transplant were stabilized in RNAlater, couriered overnight at ambient temperature to the central laboratory, and processed (29 hour workflow) using microarrays to assess T cell-mediated and antibody-mediated rejection (TCMR, ABMR). Of 538 biopsies submitted, 519 (96%) were sufficient for microarray analysis (average length 3mm)...
April 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28447927/unexpected-positive-prospective-crossmatches-in-organ-transplant
#3
REVIEW
Judith Desoutter, Marie-Joelle Apithy, Nicolas Guillaume
Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complement-dependent cytotoxicity assays and/or flow cytometry-based methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28447925/luminex-solid-phase-crossmatch-for-de-novo-donor-specific-antibodies-in-living-donor-related-transplants
#4
Sonia Mehrotra, Raj Kumar Sharma, Mahabaleshwar Mayya, Amit Gupta, Narayan Prasad, Anupma Kaul, Dharmendra Singh Bhadauria
OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121 recipients in our study group, 26 (21...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#5
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#6
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445619/mtor-inhibitors-and-risk-for-chronic-antibody-mediated-rejection-after-kidney-transplantation-where-are-we-now
#7
REVIEW
Philippe Grimbert, Olivier Thaunat
Antibody-mediated rejection (AMR) usually starts with generation of donor-specific anti-HLA antibodies (DSA), arising from a B-cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling pathway involved in AMR-related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo. In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dnDSA) or AMR - regardless of the type of regimen - is patient adherence...
April 26, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28444814/chronic-antibody-mediated-rejection-in-nonhuman-primate-renal-allografts-validation-of-human-histological-and-molecular-phenotypes
#8
B A Adam, R N Smith, I A Rosales, M Matsunami, B Afzali, T Oura, A B Cosimi, T Kawai, R B Colvin, M Mengel
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded (FFPE) samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously-described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, CAV1), derived from 10-fold cross-validation ROC curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (AUC=0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28421272/-the-pathology-of-adverse-events-with-immune-checkpoint-inhibitors
#9
V H Koelzer, K Glatz, L Bubendorf, A Weber, A Gaspert, G Cathomas, A Lugli, A Zippelius, W Kempf, K D Mertz
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs...
April 18, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28419995/hemolytic-uremic-syndrome-and-kidney-transplantation-a-case-series-and-review-of-the-literature
#10
Sabrina Milan Manani, Grazia Maria Virzì, Anna Giuliani, Anna Clementi, Alessandra Brocca, Daniela Dissegna, Francesca Martino, Emanuele Stefano Giovanni d'Amore, Claudio Ronco
BACKGROUND: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation...
April 19, 2017: Nephron
https://www.readbyqxmd.com/read/28407877/simultaneous-liver-kidney-transplantation-shifting-renal-allograft-gene-expression-from-inflammation-toward-preservation
#11
Mark Haas
Exposure of renal allografts to donor-specific antibodies activates many proinflammatory genes, resulting in antibody-mediated rejection. Simultaneous liver transplantation reduces the development of antibody-mediated rejection in renal grafts exposed to donor-specific antibodies. A study by Taner et al. in this issue of Kidney International shows this effect of the liver to involve more than simply absorbing donor-specific antibodies, with a shift in the pattern of gene expression in the kidney away from proinflammatory toward preservation of tissue function...
May 2017: Kidney International
https://www.readbyqxmd.com/read/28405599/absence-of-intragraft-b-cells-in-rejection-biopsies-after-rituximab-induction-therapy-consequences-for-clinical-outcome
#12
Martijn W F van den Hoogen, Eric J Steenbergen, Marije C Baas, Sandrine Florquin, Luuk B Hilbrands
BACKGROUND: The pathophysiological role of intragraft B cells during renal allograft rejection is unclear. METHODS: We studied B-cell infiltration during acute rejection in 53 patients who participated in a clinical trial in which adult renal transplant patients were randomized between a single intraoperative dose of rituximab (375 mg/m(2)) or placebo as induction therapy. Two independent pathologists scored all biopsies in a blinded fashion according to the Banff classification and scored for the presence of B cells and plasma cells using CD79a and CD138 as markers...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28403566/outcomes-and-risk-stratification-for-late-antibody-mediated-rejection-in-recipients-of-abo-incompatible-kidney-transplants
#13
Bonnie E Lonze, Sunjae Bae, Edward S Kraus, Mary J Holechek, Karen E King, Nada Alachkar, Fizza F Naqvi, Nabil N Dagher, Adnan Sharif, Niraj M Desai, Dorry L Segev, Robert A Montgomery
The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA-incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR...
April 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28396194/the-use-of-kinase-inhibitors-in-solid-organ-transplantation
#14
REVIEW
S Dholakia, J E Fildes, P J Friend
INTRODUCTION: Despite the efficacy of current immunosuppression regimes used in solid organ transplantation, graft dysfunction, graft lost and antibody-mediated rejection continue to be problematic. As a result, clear attraction in exploiting key potential targets controlled by kinase phosphorylation has led to a number of studies exploring the use of these drugs in transplantation. Aim In this review, we consider the role of tyrosine kinase as a target in transplantation and summarize the relevant studies on kinase inhibitors that have been reported to date...
March 25, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28393447/anti-cd40-antibody-mediated-costimulation-blockade-promotes-long-term-survival-of-deep-lamellar-porcine-corneal-grafts-in-non-human-primates
#15
Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Mee Kum Kim, Won Ryang Wee
BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28390683/prognostic-utility-of-right-ventricular-free-wall-strain-in-low-risk-patients-after-orthotopic-heart-transplantation
#16
Amr F Barakat, Brett W Sperry, Randall C Starling, Amgad Mentias, Zoran B Popovic, Brian P Griffin, Milind Y Desai
Global longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive measure of regional left and right ventricular (LV and RV) dysfunction, before onset of overt systolic dysfunction. We sought to evaluate the prognostic utility of measuring LV-GLS and RV free wall strain (FWS) in low risk patients at 1 year after orthotopic heart transplantation (OHT). We retrospectively studied 96 OHT recipients (age 52 ± 14 years, 64% men) free of antibody-mediated rejection or moderate to severe coronary allograft vasculopathy (CAV, grade 2 to 3) at 1 year after transplant...
March 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28378521/defining-the-immunogenicity-and-antigenicity-of-hla-epitopes-is-crucial-for-optimal-epitope-matching-in-clinical-renal-transplantation
#17
REVIEW
C S M Kramer, D L Roelen, S Heidt, F H J Claas
Transplantation of an human leukocyte antigen (HLA) mismatched graft can lead to the development of donor-specific antibodies (DSA), which can result in antibody mediated rejection and graft loss as well as complicate repeat transplantation. These DSA are induced by foreign epitopes present on the mismatched HLA antigens of the donor. However, not all epitopes appear to be equally effective in their ability to induce DSA. Understanding the characteristics of HLA epitopes is crucial for optimal epitope matching in clinical transplantation...
April 5, 2017: HLA
https://www.readbyqxmd.com/read/28373996/not-all-antibodies-are-created-equal-factors-that-influence-antibody-mediated-rejection
#18
REVIEW
Carrie L Butler, Nicole M Valenzuela, Kimberly A Thomas, Elaine F Reed
Consistent with Dr. Paul Terasaki's "humoral theory of rejection" numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR) and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28372986/assessing-the-potential-of-angiotensin-ii-type-1-receptor-and-donor-specific-anti-endothelial-cell-antibodies-to-predict-long-term-kidney-graft-outcome
#19
David F Pinelli, John J Friedewald, Kelley M K Haarberg, Shree L Radhakrishnan, Jennifer R Zitzner, Wendy Wegner, Anat R Tambur
Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to Angiotensin II - Type 1 Receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years...
March 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/28367453/de-novo-donor-specific-hla-antibodies-developing-early-or-late-after-transplant-are-associated-with-the-same-risk-of-graft-damage-and-loss-in-nonsensitized-kidney-recipients
#20
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago, Antonella Gurrado, Ilaria Guido, Francesca Compagno, Giacomo Garibotto, Catherine Klersy, Enrico Verrina, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, Fabrizio Ginevri
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24...
2017: Journal of Immunology Research
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