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https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#1
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
#2
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
#3
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...
August 22, 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
#4
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
#5
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
#6
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...
May 29, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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 human leukocyte antigens (HLA) remains a significant immunologic barrier to successful transplantation. Identifying immune mechanisms responsible for antibody-mediated rejection (ABMR) is an important goal. Here we explored the possibility of predicting the risk for ABMR by measuring mRNA transcripts of ABMR-associated genes in plasma exosomes from kidney transplant patients. METHODS: Total RNA was extracted from exosomes purified from 152 EDTA-plasma samples of 64 patients (18 ABMR, 8 cell-mediated rejection [CMR], 38 no rejection in desensitized (DES) and non-desensitized (non-DES) control groups) for reverse transcription into cDNA, preamplification and then real time quantitative polymerase chain reaction (qPCR) for 21 candidate genes...
May 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28449409/real-time-central-assessment-of-kidney-transplant-indication-biopsies-by-microarrays-the-intercomex-study
#15
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/28255562/treatment-of-antibody-mediated-renal-allograft-rejection-improving-step-by-step
#16
Nils Lachmann, Michael Duerr, Constanze Schönemann, Axel Pruß, Klemens Budde, Johannes Waiser
Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR). Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg), low-dose (30 g) intravenous immunoglobulins (IVIG), and plasmapheresis (PPH, 6x) (group RLP, n = 12). Between 2009 and June 2010, patients received bortezomib (1.3 mg/m(2), 4x) together with low-dose IVIG and PPH (group BLP, n = 11)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28255002/antibody-mediated-rejection-due-to-preexisting-versus-de-novo-donor-specific-antibodies-in-kidney-allograft-recipients
#17
COMPARATIVE STUDY
Olivier Aubert, Alexandre Loupy, Luis Hidalgo, Jean-Paul Duong van Huyen, Sarah Higgins, Denis Viglietti, Xavier Jouven, Denis Glotz, Christophe Legendre, Carmen Lefaucheur, Philip F Halloran
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205)...
June 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28245084/donor-specificity-but-not-broadness-of-sensitization-is-associated-with-antibody-mediated-rejection-and-graft-loss-in-renal-allograft-recipients
#18
C Wehmeier, G Hönger, H Cun, P Amico, P Hirt-Minkowski, A Georgalis, H Hopfer, M Dickenmann, J Steiger, S Schaub
Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105)...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226404/the-effect-of-cortex-medulla-proportions-on-molecular-diagnoses-in-kidney-transplant-biopsies-rejection-and-injury-can-be-assessed-in-medulla
#19
K S Madill-Thomsen, R C Wiggins, F Eskandary, G A Böhmig, P F Halloran
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28166393/donor-specific-antibodies-c1q-binding-improvement-in-kidney-graft-management
#20
COMMENT
Sylvie Ferrari-Lacraz
No abstract text is available yet for this article.
April 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
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