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hla antibodies transplantation

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https://www.readbyqxmd.com/read/28088367/assignment-of-c1q-binding-hla-antibodies-as-unacceptable-hla-antigens-avoids-positive-cdc-crossmatches-prior-to-transplantation-of-deceased-donor-organs
#1
David Juhl, Matthias Marget, Michael Hallensleben, Siegfried Görg, Malte Ziemann
Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed...
January 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#2
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28065559/post-listing-survival-for-highly-sensitised-patients-on-the-uk-kidney-transplant-waiting-list-a-matched-cohort-analysis
#3
Miriam Manook, Leonardo Koeser, Zubir Ahmed, Matthew Robb, Rachel Johnson, Olivia Shaw, Nicos Kessaris, Anthony Dorling, Nizam Mamode
BACKGROUND: More than 40% of patients awaiting a kidney transplant in the UK are sensitised with human leucocyte antigen (HLA) antibodies. Median time to transplantation for such patients is double that of unsensitised patients at about 74 months. Removing antibody to perform an HLA-incompatible (HLAi) living donor transplantation is perceived to be high risk, although patient survival data are limited. We compared survival of patients opting for an HLAi kidney transplant with that of similarly sensitised patients awaiting a compatible organ...
January 5, 2017: Lancet
https://www.readbyqxmd.com/read/28058698/high-soluble-cd30-levels-and-associated-anti-hla-antibodies-in-patients-with-failed-renal-allografts
#4
Gonca E Karahan, Yasar Caliskan, Kursat Ozdilli, Cigdem Kekik, Huseyin Bakkaloglu, Bahar Caliskan, Aydin Turkmen, Mehmet S Sever, Fatma S Oguz
INTRODUCTION: Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. METHODS: 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study...
December 26, 2016: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#5
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28058219/impact-of-preformed-donor-specific-antibodies-against-hla-class-i-on-kidney-graft-outcomes-comparative-analysis-of-exclusively-anti-cw-vs-anti-a-and-or-b-antibodies
#6
Sofia Santos, Jorge Malheiro, Sandra Tafulo, Leonídio Dias, Rute Carmo, Susana Sampaio, Marta Costa, Andreia Campos, Sofia Pedroso, Manuela Almeida, La Salete Martins, Castro Henriques, António Cabrita
AIM: To analyze the clinical impact of preformed antiHLA-Cw vs antiHLA-A and/or -B donor-specific antibodies (DSA) in kidney transplantation. METHODS: Retrospective study, comparing 12 patients transplanted with DSA exclusively antiHLA-Cw with 23 patients with preformed DSA antiHLA-A and/or B. RESULTS: One year after transplantation there were no differences in terms of acute rejection between the two groups (3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1)...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28052334/association-of-hla-drb1-and-hla-dqb1-with-red-blood-cell-alloimmunization-in-the-czech-population
#7
A Maluskova, F Mrazek, M Pauliskova, P Kovarova, M Koristka, P Jindra, Z Cermakova
BACKGROUND AND OBJECTIVES: Alloimmune antibodies against red-blood-cell (RBC) antigens induced in susceptible individuals (responders) by transfusion, pregnancy or transplantation may have serious clinical consequences. The aim of this study was to investigate association of alloimmunization against selected RBC antigens with HLA-Class II. MATERIALS AND METHODS: A total of 230 responders (106 monoresponders and 124 multiresponders) were enrolled into the study. HLA-DRB1 and HLA-DQB1 variants were determined by PCR-SSO and their frequencies compared between the patients (patient subgroups) and 375 ethnically and regionally matched controls...
January 4, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28027625/early-conversion-from-calcineurin-inhibitor-to-everolimus-based-therapy-following-kidney-transplantation-results-of-the-randomized-elevate-trial
#8
Johan W de Fijter, Hallvard Holdaas, Ole Øyen, Jan-Stephan Sanders, Sankaran Sundar, Frederike J Bemelman, Claudia Sommerer, Julio Pascual, Yingyos Avihingsanon, Cholatip Pongskul, Frederic Oppenheimer, Lorenzo Toselli, Graeme Russ, Zailong Wang, Patricia Lopez, Jossy Kochuparampil, Josep M Cruzado, Markus van der Giet
In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated GFR from randomization to month 12, was similar for everolimus versus CNI: mean (SE) 0.3(1.5)mL/min/1.73(2) versus -1.5(1.5)mL/min/1.73(2) (p=0.116). At month 24, mean (SD) estimated GFR was 62...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#9
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28024930/urine-fibrosis-markers-and-risk-of-allograft-failure-in-kidney-transplant-recipients-a-case-cohort-ancillary-study-of-the-favorit-trial
#10
Joachim H Ix, Ronit Katz, Nisha Bansal, Meredith Foster, Daniel E Weiner, Russell Tracy, Vasantha Jotwani, Jan Hughes-Austin, Dianne McKay, Francis Gabbai, Chi-Yuan Hsu, Andrew Bostom, Andrew S Levey, Michael G Shlipak
BACKGROUND: Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown. STUDY DESIGN: Case-cohort study. SETTING & PARTICIPANTS: The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients...
December 23, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28018342/detection-of-hla-antibodies-in-organ-transplant-recipients-triumphs-and-challenges-of-the-solid-phase-bead-assay
#11
REVIEW
Brian D Tait
This review outlines the development of human leukocyte antigen (HLA) antibody detection assays and their use in organ transplantation in both antibody screening and crossmatching. The development of sensitive solid phase assays such as the enzyme-linked immunosorbent assay technique, and in particular the bead-based technology has revolutionized this field over the last 10-15 years. This revolution however has created a new paradigm in clinical decision making with respect to the detection of low level pretransplant HLA sensitization and its clinical relevance...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#12
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/28005572/polyreactive-natural-antibodies-in-transplantation
#13
Emmanuel Zorn, Sarah B See
PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28003816/hla-mismatching-strategies-for-solid-organ-transplantation-a-balancing-act
#14
REVIEW
Andrea A Zachary, Mary S Leffell
HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27995324/hla-epitope-matching-in-pediatric-renal-transplantation
#15
Matthew P Sypek, Peter Hughes, Joshua Y Kausman
Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications...
December 19, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27993881/flow-cytometric-panel-reactive-antibody-results-and-the-ability-to-find-transfusion-compatible-platelets-after-antibody-desensitization-for-allogeneic-bone-marrow-transplant
#16
Eric R Rosenbaum, Soumya Pandey, Terry O Harville, Gina A Drobena, Michele Cottler-Fox
BACKGROUND: Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRA(®) and Luminex(®) based Single Antigen Bead (SAB)] would also correlate with the ability to find compatible platelets for allosensitized recipients. METHODS: A female patient with myelodysplastic syndrome and a high HLA class I PRA [>90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT...
December 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27990486/successful-simultaneous-liver-kidney-transplantation-in-the-presence-of-multiple-high-titered-class-i-and-ii-antidonor-hla-antibodies
#17
Flavio Paterno, Alin Girnita, Paul Brailey, David Witte, Jiang Wang, Madison C Cuffy, Tayyab Diwan, Simon Tremblay, Jane Y Revollo, Rita R Alloway, Michael R Schoech, Nadim Anwar, Shimul A Shah, Steve E Woodle
The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27990485/the-association-between-broad-antigen-hla-mismatches-eplet-hla-mismatches-and-acute-rejection-after-kidney-transplantation
#18
Hung Thanh Do Nguyen, Germaine Wong, Jeremy R Chapman, Stephen P McDonald, Patrick T Coates, Narelle Watson, Graeme R Russ, Lloyd D'Orsogna, Wai Hon Lim
BACKGROUND: Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients. METHODS: The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27979771/rapid-and-strong-de-novo-donor-specific-antibody-development-in-a-lung-transplant-recipient-short-communication-case-report
#19
Andrew L Lobashevsky, Kevin M Rosner, John D May, Michael D Duncan, Chadi A Hage, Erin N Lushin, Eve E Anderson, David W Roe
A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations. Twinrix, Zostavax and MMR vaccines contain viruses grown on live human lung fibroblasts (MRC-5, typed B*07:02, 44:02, and WI-38, typed B*08:01, 58:01)...
December 12, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27973391/a-3-center-study-reveals-new-insights-into-the-impact-of-nonhla-antibodies-on-lung-transplantation-outcome
#20
Nancy L Reinsmoen, James Mirocha, Christopher R Ensor, Marilyn Marrari, George Chaux, Deborah J Levine, Xiaohai Zhang, Adriana Zeevi
BACKGROUND: The presence of antibodies to angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1R and ETAR antibodies on graft outcome in lung transplantation. METHODS: Pre and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1R and ETAR by the ELISA assay...
August 4, 2016: Transplantation
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