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https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#1
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29109529/glomerulocapillary-mirna-response-to-hla-class-i-antibody-in-vitro-and-in-vivo
#2
Falko M Heinemann, Peter T Jindra, Clemens L Bockmeyer, Philip Zeuschner, Juliane Wittig, Heike Höflich, Marc Eßer, Mahmoud Abbas, Georg Dieplinger, Katharina Stolle, Udo Vester, Peter F Hoyer, Stephan Immenschuh, Andreas Heinold, Peter A Horn, Wentian Li, Ute Eisenberger, Jan U Becker
Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#3
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28949089/treatment-of-chronic-antibody-mediated-rejection-with-intravenous-immunoglobulins-and-rituximab-a-multicenter-prospective-randomized-double-blind-clinical-trial
#4
Francesc Moreso, Marta Crespo, Juan C Ruiz, Armando Torres, Alex Gutierrez-Dalmau, Antonio Osuna, Manel Perelló, Julio Pascual, Irina B Torres, Dolores Redondo-Pachón, Emilio Rodrigo, Marcos Lopez-Hoyos, Daniel Seron
There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m(2) and/or severe interstitial fibrosis/tubular atrophy were excluded...
September 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#5
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28929636/risk-factors-for-the-development-of-antibody-mediated-rejection-in-highly-sensitized-pediatric-kidney-transplant-recipients
#6
Irene K Kim, Jua Choi, Ashley Vo, Alexis Kang, Justin Steggerda, Sabrina Louie, Mark Haas, James Mirocha, J Louis Cohen, Helen Pizzo, Elaine S Kamil, Stanley C Jordan, Dechu Puliyanda
ABMR remains a significant concern for early graft loss, especially for those who are HS against HLA antigens. We sought to determine the risk factors leading to ABMR in HS pediatric kidney transplant recipients. From January 2009 to December 2015, 16 HS pediatric kidney transplant patients at our center (age range 2-21) were retrospectively reviewed for outcomes and risk factors for ABMR. All HS patients received desensitization with high-dose IVIG/rituximab prior to transplant. Two groups were examined: ABMR(+) (n = 7) and ABMR(-) (n = 9)...
September 19, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#7
REVIEW
Neetika Garg, Milagros D Samaniego, Dana Clark, Arjang Djamali
The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause)...
August 15, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28858176/midterm-outcomes-of-12-renal-transplant-recipients-treated-with-eculizumab-to-prevent-atypical-hemolytic-syndrome-recurrence
#8
Charlène Levi, Véronique Frémeaux-Bacchi, Julien Zuber, Marion Rabant, Magali Devriese, Renaud Snanoudj, Anne Scemla, Lucile Amrouche, Arnaud Mejean, Christophe Legendre, Rebecca Sberro-Soussan
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab. METHODS: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25)...
August 25, 2017: Transplantation
https://www.readbyqxmd.com/read/28833936/persistent-c4d-and-antibody-mediated-rejection-in-pediatric-renal-transplant-patients
#9
Andrew M South, Lynn Maestretti, Neeraja Kambham, Paul C Grimm, Abanti Chaudhuri
Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow-up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12 months was a composite of ≥50% reduction in eGFR, transplant glomerulopathy, or graft failure...
November 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#10
J A Steggerda, A Kang, S-H Pan, V Sundaram, N N Nissen, A S Klein, T Todo, A Annamalai, A Vo, S C Jordan, I K Kim
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28664838/treatment-of-antibody-mediated-rejection-of-kidney-grafts-with-bortezomib-and-or-rituximab-compared-to-standard-regimen-experience-of-slovene-national-center
#11
Teja Oblak, Jelka Lindič, Jakob Gubenšek, Radoslav Kveder, Andreja Aleš Rigler, Andrej Škoberne, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin, Rafael Ponikvar, Gregor Mlinšek, Dušan Ferluga, Nika Kojc, Uroš Godnov, Damjan Kovač
BACKGROUND: The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab. METHODS: The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 - 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab...
2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28662985/building-a-tissue-based-molecular-diagnostic-system-in-heart-transplant-rejection-the-heart-molecular-microscope-diagnostic-mmdx-system
#12
Philip F Halloran, Luciano Potena, Jean-Paul Duong Van Huyen, Patrick Bruneval, Ornella Leone, Daniel H Kim, Xavier Jouven, Jeff Reeve, Alexandre Loupy
BACKGROUND: The emergence of molecular systems offers opportunities for improving the assessment of rejection in heart transplant biopsy specimens. The present study developed a microarray-based system for assessing heart transplant endomyocardial biopsy (EMB) specimens. METHODS: We analyzed 331 protocol or for-cause EMB specimens from 221 subjects in 3 centers (Edmonton, Bologna, and Paris). Unsupervised principal component analysis (PCA) and archetype analysis used rejection-associated transcripts (RATs) shown in kidney transplants to be associated with antibody-mediated rejection (ABMR) or T cell-mediated rejection (TCMR), or both...
November 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28654684/intravenous-immunoglobulin-therapy-in-kidney-transplant-recipients-with-de-novo-dsa-results-of-an-observational-study
#13
Marie Matignon, Caroline Pilon, Morgane Commereuc, Cynthia Grondin, Claire Leibler, Tomek Kofman, Vincent Audard, José Cohen, Florence Canoui-Poitrine, Philippe Grimbert
BACKGROUND: Approximately 25% of kidney transplant recipients develop de novo anti-HLA donor-specific antibodies (dnDSA) leading to acute antibody-mediated rejection (ABMR) in 30% of patients. Preemptive therapeutic strategies are not available. METHODS: We conducted a prospective observational study including 11 kidney transplant recipients. Inclusion criteria were dnDSA occurring within the first year after transplant and normal allograft biopsy. All patients were treated with high-dose IVIG (2 g/kg 0, 1 and 2 months post-dnDSA)...
2017: PloS One
https://www.readbyqxmd.com/read/28654216/mechanistic-sharing-between-nk-cells-in-abmr-and-effector-t-cells-in-tcmr
#14
M D Parkes, P F Halloran, L G Hidalgo
Human organ allograft rejection depends on effector lymphocytes: NK cells in antibody-mediated rejection (ABMR) and effector T cells in T cell-mediated rejection (TCMR). We hypothesized that NK cell CD16a stimulation and CD8 T cell TCR/CD3 stimulation represent highly similar effector systems, and should lead to shared molecular changes between ABMR and TCMR. We studied similarity between soluble proteins and the transcripts induced in CD16a stimulated NK cells and TCR/CD3-stimulated T cells in vitro. Of 30 soluble mediators tested, CD16a-activated NK cells and CD3/TCR activated T cells produced the same limited set of five mediators-CCL3, CCL4, CSF2, IFNG, and TNF-and failed to produce 25 others...
June 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28614805/assessing-rejection-related-disease-in-kidney-transplant-biopsies-based-on-archetypal-analysis-of-molecular-phenotypes
#15
Jeff Reeve, Georg A Böhmig, Farsad Eskandary, Gunilla Einecke, Carmen Lefaucheur, Alexandre Loupy, Philip F Halloran
Conventional histologic diagnosis of rejection in kidney transplants has limited repeatability due to its inherent requirement for subjective assessment of lesions, in a rule-based system that does not acknowledge diagnostic uncertainty. Molecular phenotyping affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems and quantify levels of uncertainty. Microarray data from 1,208 kidney transplant biopsies were collected prospectively from 13 centers...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614191/anti-cd20-blocker-rituximab-in-kidney-transplantation
#16
Puneet Sood, Sundaram Hariharan
Rituximab is a chimeric anti-CD20 monoclonal protein used in various clinical scenarios in kidney transplant recipients. However, its evidence-based use there remains limited due to lack of controlled studies, limited sample size, short follow-up and poorly defined endpoints. Rituximab is indicated for CD20+ PTLD. It may be beneficial for treating recurrent MN and recurrent allograft ANCA vasculitis and possibly for recurrent FSGS. Rituximab, in combination with IVIG/PP, appears to decrease antibody level and increase the odds of transplantation in sensitized recipients...
June 13, 2017: Transplantation
https://www.readbyqxmd.com/read/28601127/increase-in-spot-urine-protein-excretion-is-associated-with-late-kidney-graft-rejection-and-predicts-rejection-phenotype
#17
Miha Arnol, Manca Oblak, Gregor Mlinšek, Jelka Lindič, Aljoša Kandus, Dušan Ferluga, Nika Kojc, Jadranka Buturović-Ponikvar
AIMS: A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. METHODS: 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%)...
June 9, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28594750/blockade-of-hla-antibody-triggered-classical-complement-activation-in-sera-from-subjects-dosed-with-the-anti-c1s-monoclonal-antibody-tnt009-results-from-a-randomized-first-in-human-phase-1-trial
#18
Jakob Mühlbacher, Bernd Jilma, Markus Wahrmann, Johann Bartko, Farsad Eskandary, Christian Schörgenhofer, Michael Schwameis, Graham C Parry, James C Gilbert, Sandip Panicker, Georg A Böhmig
BACKGROUND: Complement may play a key role in antibody-mediated rejection (ABMR). A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. METHODS: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n=48; 7 consecutive cohorts: 0...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28565830/correlation-between-pkb-akt-gsk-3%C3%AE-expression-and-tubular-epithelial-mesenchymal-transition-in-renal-allografts-with-chronic-active-antibody-mediated-rejection
#19
Qiang Yan, Hao Luo, Baoyao Wang, Weiguo Sui, Guimian Zou, Huaizhou Chen, Hequn Zou
Chronic antibody-mediated rejection (ABMR) is a major cause of the transplant renal interstitial fibrosis and transplanted kidney epithelial cell transdifferentiation is one of the main mechanisms. The transforming growth factor (TGF)-β1/integrin-linked kinase (ILK) signaling pathway has a significant role in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells; however, the molecular mechanisms of this process have remained elusive. The present study confirmed that Akt and glycogen synthase kinase (GSK)-3β, as TGF-β1 downstream signaling factors, are involved in fibrotic processes caused by kidney disease, which, however, has been rarely reported in the kidney transplant field...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28557957/plasma-exosomes-from-hla-sensitized-kidney-transplant-recipients-contain-mrna-transcripts-which-predict-development-of-antibody-mediated-rejection
#20
Hao Zhang, Edmund Huang, Joseph Kahwaji, Cynthia C Nast, Ping Li, James Mirocha, David L Thomas, Shili Ge, Ashley A Vo, Stanley C Jordan, Mieko Toyoda
BACKGROUND: Sensitization to HLA remains a significant immunologic barrier to successful transplantation. Identifying immune mechanisms responsible for antibody-mediated rejection (AMR) is an important goal. Here, we explored the possibility of predicting the risk for AMR by measuring mRNA transcripts of AMR-associated genes in plasma exosomes from kidney transplant patients. METHODS: Total RNA was extracted from exosomes purified from 152 ethylenediaminetetraacetic acid-plasma samples of 64 patients (18 AMR, 8 cell-mediated rejection [CMR], 38 no rejection in desensitized [DES] and non-DES control groups) for reverse transcription into cDNA, preamplification and then real time quantitative polymerase chain reaction (qPCR) for 21 candidate genes...
October 2017: Transplantation
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