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https://www.readbyqxmd.com/read/27888573/b-cell-activating-factor-baff-a-predictor-of-antibody-mediated-rejection-in-kidney-transplantation-recipients
#1
Wannarat Pongpirul, Wiwat Chancharoenthana, Krit Pongpirul, Asada Leelahavanichakul, Wipawee Kittikowit, Kamonwan Jutivorakool, Bunthoon Nonthasoot, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa, Natavudh Townamchai
BACKGROUND: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection...
November 26, 2016: Nephrology
https://www.readbyqxmd.com/read/27500255/early-and-sustained-reduction-in-donor-specific-antibodies-in-desensitized-living-donor-kidney-transplant-recipients-a-3-year-prospective-study
#2
David Shaffer, Irene D Feurer, Deborah Crowe, Heidi Schaefer
BACKGROUND: Desensitization with IVIG and rituximab allows acceptable graft survival in sensitized kidney transplant recipients with preexisting donor-specific antibodies (DSAs) and a positive crossmatch. There is little published data reporting the durability of DSA removal in kidney transplant recipients treated with IVIG and rituximab. METHODS: We conducted a 3-year prospective DSA monitoring study in living donor kidney recipients with preexisting DSA to assess the durability of DSA removal after a perioperative protocol of IVIG and rituximab...
February 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27495776/conformational-variants-of-the-individual-hla-i-antigens-on-luminex-single-antigen-beads-used-in-monitoring-hla-antibodies-problems-and-solutions
#3
Vadim Jucaud, Mepur H Ravindranath, Paul I Terasaki
BACKGROUND: Single antigen beads (SAB) are used for monitoring HLA antibodies in pre- and post-transplant patients despite the discrepancy between virtual and actual crossmatch results and transplant outcomes. This discrepancy can be attributed to the presence of conformational variants of HLA-I on SAB, assessment of which would increase the concordance between SAB and flow cytometry crossmatch (FCXM) results, thus enabling improved organ accessibility for the waiting list patients and a better prediction of AMR...
August 5, 2016: Transplantation
https://www.readbyqxmd.com/read/27196533/immunogenicity-of-anti-hla-antibodies-in-pancreas-and-islet-transplantation
#4
Benjamin Chaigne, Kirsten Geneugelijk, Benoît Bédat, Mohamed Alibashe Ahmed, Gideon Hönger, Sophie de Seigneux, Sandrine Demuylder-Mischler, Thierry Berney, Eric Spierings, Sylvie Ferrari-Lacraz, Jean Villard
The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity and anti-HLA antibody characteristic were collected. Between January 2008 and July 2014, 18 patients received islet transplants and 26 patients received a pancreas transplant...
May 18, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27188713/a-new-data-driven-model-for-post-transplant-antibody-dynamics-in-high-risk-kidney-transplantation
#5
Yan Zhang, David Briggs, David Lowe, Daniel Mitchell, Sunil Daga, Nithya Krishnan, Robert Higgins, Natasha Khovanova
The dynamics of donor specific human leukocyte antigen antibodies during early stage after kidney transplantation are of great clinical interest as these antibodies are considered to be associated with short and long term clinical outcomes. The limited number of antibody time series and their diverse patterns have made the task of modelling difficult. Focusing on one typical post-transplant dynamic pattern with rapid falls and stable settling levels, a novel data-driven model has been developed for the first time...
May 14, 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/27037650/the-leuven-immunomodulatory-protocol-promotes-t-regulatory-cells-and-substantially-prolongs-survival-after-first-intestinal-transplantation
#6
Laurens J Ceulemans, Faouzi Braza, Diethard Monbaliu, Ina Jochmans, Gert De Hertogh, Johannie Du Plessis, Marie-Paule Emonds, Hiroaki Kitade, Masaru Kawai, Ying Li, Zhao Xiangdong, Takaaki Koshiba, Ben Sprangers, Sophie Brouard, Mark Waer, Jacques Pirenne
Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug-toxicity). We developed in the lab the Leuven Immunomodulatory Protocol (LIP) and translated it to the clinics. LIP consists in experimentally-proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: Donor-Specific-Blood-Transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; minimizing reperfusion-injury and endotoxin-translocation...
April 1, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26801944/management-of-sensitized-pediatric-patients-prior-to-renal-transplantation
#7
Kwanchai Pirojsakul, Dev Desai, Chantale Lacelle, Mouin G Seikaly
BACKGROUND: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. METHODS: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %...
October 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/26494958/clinical-significance-of-donor-specific-human-leukocyte-antigen-antibodies-in-liver-transplantation
#8
REVIEW
Antonio Cuadrado, David San Segundo, Marcos López-Hoyos, Javier Crespo, Emilio Fábrega
Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported...
October 21, 2015: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/26303035/de-novo-donor-specific-anti-hla-antibodies-mediated-rejection-in-liver-transplant-patients
#9
Arnaud Del Bello, Nicolas Congy-Jolivet, Marie Danjoux, Fabrice Muscari, Laurence Lavayssière, Laure Esposito, Isabelle Cardeau-Desangles, Joëlle Guitard, Gaëlle Dörr, David Milongo, Bertrand Suc, Jean Pierre Duffas, Laurent Alric, Christophe Bureau, Céline Guilbeau-Frugier, Lionel Rostaing, Nassim Kamar
The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1...
December 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/26281144/late-antibody-mediated-rejection-in-a-large-prospective-cross-sectional-study-of-kidney-allograft-recipients-preliminary-results-of-the-screening-phase-of-the-borteject-trial
#10
RANDOMIZED CONTROLLED TRIAL
Farsad Eskandary, Gregor Bond, Heinz Regele, Nicolas Kozakowski, Zeljko Kikić, Markus Wahrmann, Helmuth Haslacher, Rainer Oberbauer, Vido Ramassar, Philip Halloran, Georg A Böhmig
There is limited data on the rate of late antibody-mediated rejection (ABMR) in unselected transplant cohorts. Here, we investigated the prevalence and characteristics of ABMR in a large cohort of long-term kidney allograft recipients. Patients were screened in the context of a randomized controlled trial (BORTEJECT study; ClinicalTrials.gov: NCT01873157) designed to investigate the impact of bortezomib on the course of late ABMR. The study (initiation in October 2013) includes a cross-sectional ABMR screening (key inclusion criterion: functioning graft at ≥ 180 days) to identify 44 recipients eligible for inclusion in the intervention trial...
2014: Clinical Transplants
https://www.readbyqxmd.com/read/26264744/subclass-analysis-of-donor-hla-specific-igg-in-antibody-incompatible-renal-transplantation-reveals-a-significant-association-of-igg4-with-rejection-and-graft-failure
#11
Natasha Khovanova, Sunil Daga, Torgyn Shaikhina, Nithya Krishnan, James Jones, Daniel Zehnder, Daniel Mitchell, Robert Higgins, David Briggs, David Lowe
Donor HLA-specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan-IgG level and at 30 days post-transplantation in eighty HLA antibody-incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody-mediated rejection (P = 0...
December 2015: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/26118475/detection-of-alloantibody-mediated-complement-activation-a-diagnostic-advance-in-monitoring-kidney-transplant-rejection
#12
REVIEW
Georg A Böhmig, Zeljko Kikic, Markus Wahrmann, Farsad Eskandary, Arezu Z Aliabadi, Gerhard J Zlabinger, Heinz Regele, Helmut E Feucht
OBJECTIVE: Antibody-mediated rejection (ABMR) is an important cause of kidney allograft injury. In the last two decades, detection of complement split product C4d along transplant capillaries, a footprint of antibody-mediated classical complement activation, has evolved as a useful diagnostic marker of ABMR. While it was recognized that ABMR may occur also in the absence of C4d, numerous studies have shown that C4d deposition may indicate a more severe rejection phenotype associated with poor graft survival...
March 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/26116896/pregnancy-induced-hla-antibodies-respond-more-vigorously-after-renal-transplantation-than-antibodies-induced-by-prior-transplantation
#13
Rob Higgins, David Lowe, Sunil Daga, Mark Hathaway, C Williams, F T Lam, Habib Kashi, Lam Chin Tan, Chris Imray, Simon Fletcher, Nithya Krishnan, Pat Hart, Daniel Zehnder, David Briggs
Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870)...
August 2015: Human Immunology
https://www.readbyqxmd.com/read/25758878/non-tolerability-of-double-filtration-plasmapheresis-in-antibody-incompatible-kidney-transplant-candidates
#14
MULTICENTER STUDY
Hadia Hebibi, Hugo Weclawiak, Lionel Rostaing, Séverine Beaudreuil, Asma Allal, Hélène François, Antoine Durrbach, Nassim Kamar
Few studies have reported the use of double-filtration plasmapheresis (DFPP) in antibody-incompatible kidney transplantation. To assess the efficiency and tolerability of DFPP, we prospectively studied four chronic hemodialysis patients from two centers undergoing antibody-incompatible kidney transplantation. DFPP was used for ABO-incompatible transplantation (n = 1), for high human leukocyte antigen (HLA) immunization levels (n = 2) or for the presence of a donor-specific antibody (DSA) against a potential living donor (n = 1)...
March 2015: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/25706884/donor-hla-specific-abs-to-bmt-or-not-to-bmt
#15
REVIEW
M S Leffell, R J Jones, D E Gladstone
The engraftment failure associated with Abs to donor-specific HLA (DSA) limits options for sensitized BMT candidates. Fourteen of fifteen patients with no other viable donor options were desensitized and transplanted using a regimen of plasmapheresis and low-dose i.v. Ig modified to accommodate pre-BMT conditioning. DSA levels were assessed by solid-phase immunoassays and cell-based crossmatch tests. DSA levels were monitored throughout desensitization and on day -1 to determine if there was any DSA rebound that would require additional treatment...
June 2015: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/25624380/eculizumab-to-treat-antibody-mediated-rejection-in-a-7-year-old-kidney-transplant-recipient
#16
Hassib Chehade, Samuel Rotman, Maurice Matter, Eric Girardin, Vincent Aubert, Manuel Pascual
We report on successful early eculizumab administration to treat acute antibody-mediated rejection (ABMR) in a highly sensitized kidney transplant recipient. The recipient is a 7-year-old boy who received, 6 months after a desensitization protocol with monthly intravenous immunoglobulin infusion, a second kidney transplant in the presence of low donor-specific antibodies (DSAs). Both pretransplant lymphocytotoxic and flow cytometric crossmatch were negative. Allograft function recovered promptly, with excellent initial function...
February 2015: Pediatrics
https://www.readbyqxmd.com/read/25565259/pre-transplant-low-level-hla-antibody-shows-a-composite-poor-outcome-in-long-term-outcome-of-renal-transplant-recipients
#17
Jun Tian, Dadong Li, Tod V Alberghini, Michael Rewinski, Ning Guo, Laurine M Bow
To determine the significance of low-level DSA (donor specific antibody) in patients transplanted with negative cytotoxicity AHG (antihuman immunoglobulin) crossmatch, data from 279 patients who received a kidney transplant between July 1999 and March 2006 were collected. All kidney recipients received ABO-compatible donors. A poor outcome was defined as any one of the following: death, Cr>2.0 mmol/L, occurrence of a rejection episode. Luminex Screening and Single Antigen assays from Tepnel Life Codes were used to detect human leukocyte antigen antibodies on pre-transplant sera retrospectively...
March 2015: Renal Failure
https://www.readbyqxmd.com/read/25534446/prospective-iterative-trial-of-proteasome-inhibitor-based-desensitization
#18
E S Woodle, A R Shields, N S Ejaz, B Sadaka, A Girnita, R C Walsh, R R Alloway, P Brailey, M A Cardi, B G Abu Jawdeh, P Roy-Chaudhury, A Govil, G Mogilishetty
A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5)...
January 2015: American Journal of Transplantation
https://www.readbyqxmd.com/read/25449536/genes-associated-with-antibody-dependent-cell-activation-are-overexpressed-in-renal-biopsies-from-patients-with-antibody-mediated-rejection
#19
Elina Suviolahti, Shili Ge, Cynthia C Nast, James Mirocha, Artur Karasyov, Molly White, Stanley C Jordan, Mieko Toyoda
INTRODUCTION: Antibody-mediated rejection (ABMR) is dependent on complement activating donor-specific anti-HLA antibodies (DSA). This is commonly detected by C4d deposition in allografts. However, recent data define a C4d negative ABMR phenotype suggesting a role for complement-independent DSA injury, antibody-dependent cellular cytotoxicity (ADCC). METHODS: Here, we established an in vitro ADCC model that identified human ADCC-activated genes using microarray analysis...
January 2015: Transplant Immunology
https://www.readbyqxmd.com/read/25242749/virtual-crossmatch-in-kidney-transplantation
#20
A Piazza, G Ozzella, E Poggi, D Caputo, A Manfreda, D Adorno
BACKGROUND: The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation...
September 2014: Transplantation Proceedings
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