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Antibody mediated rejection

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https://www.readbyqxmd.com/read/28740496/evaluation-of-antigen-specific-igm-and-igg-production-during-an-in-vitro-peripheral-blood-mononuclear-cell-culture-assay
#1
Yoshiko Matsuda, Ryoichi Imamura, Shiro Takahara
The recent attention given to diseases associated with memory B-cell (mBC)-produced antibodies (Abs) suggests the need for a similar in vitro assay to evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear cells (PBMCs) with the intent to collect mBC-derived Abs in vitro and maintain their cell-cell contact-dependent interactions with helper T-cells. PBMCs were cultured with interleukin (IL)-21, CpG-oligodeoxynucleotides (ODN), phorbol myristate acetate (PMA), and phytohemagglutinin/leucoagglutinin (PHA-L) in 24-well flat-bottom plates (5 × 10(5) cells/well)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#2
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/28735989/outcome-of-pretransplantation-therapeutic-plasma-exchange-in-highly-sensitized-deceased-donor-kidney-transplant-recipients
#3
P Tipjaiaue, A Ingsathit, P Kantachuvesiri, S Rattanasiri, D Thammanichanond, T Mongkolsuk, N Arpornsujaritkun, V Sumethkul, S Kantachuvesiri
BACKGROUND: Sensitization is associated with a high rate of post-transplantation rejection. A desensitization protocol using therapeutic plasma exchange (TPE) was proposed to reduce anti-HLA antibody before transplantation, but there has been limited data regarding the efficacy of pretransplantation TPE in highly sensitized deceased-donor kidney transplantation (DDKT). METHODS: A retrospective cohort study of 142 patients who received DDKT was conducted and divided into two groups: a high-panel-reactive antibody (PRA) >50% group and a low-PRA ≤50% group...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28732720/impact-on-mid-term-kidney-graft-outcomes-of-pretransplant-anti-hla-antibodies-detected-by-solid-phase-assays-do-donor-specific-antibodies-tell-the-whole-story
#4
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0...
July 18, 2017: Human Immunology
https://www.readbyqxmd.com/read/28731910/new-answers-to-old-conundrums-what-antibodies-exosomes-and-inflammasomes-bring-to-the-conversation-canadian-national-transplant-research-program-international-summit-report
#5
Mélanie Dieudé, Lori J West, Daniel A Muruve, Lakshman Gunaratman, Thalachallour Mohanakumar, Emmanuel Zorn, Christopher W Cairo, Darren H Freed, Kirk R Schultz, Robert L Fairchild, Marie-Josée Hébert
Antibody-mediated injury is a major cause of allograft dysfunction and loss. Antibodies to ABH(O) blood group antigens are classical mediators of ABO-incompatible (ABOi) graft rejection, while donor-specific anti-HLA antibodies and, more recently, autoantibodies are appreciated as important contributors to allograft inflammation and dysfunction. In August 2016, the International Summit of the Canadian National Transplant Research Program focused on recent advances in the field of antibody-mediated rejection...
July 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28731902/terasaki-epitope-mismatch-burden-predicts-the-development-of-de-novo-dq-donor-specific-antibodies-and-are-associated-with-adverse-allograft-outcomes
#6
Michelle Willicombe, Matthew Blow, Eva Santos-Nunez, Corinna Freeman, Paul Brookes, David Taube
BACKGROUND: De novo DQ DSA are associated with antibody-mediated rejection and allograft loss. Given the lack of effective treatment of de novo DQ DSA, their prevention is vital if there is to be an improvement of long term allograft survival. Using the HLA Matchmaker programme, DQ epitope matching has been shown to be superior to HLA antigen mismatching in predicting de novo DQ DSA development. Whether DQ epitopes determined by Terasaki may more accurately predict de novo DQ development over HLA antigen matching is not known...
July 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#7
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28723698/application-technical-issues-and-interpretation-of-c1q-for-graft-outcome
#8
Dolly B Tyan
PURPOSE OF REVIEW: Significant interest and controversy surround the use of C1q for determining risk of antibody-mediated rejection (AMR) and graft loss. Alternate models for predicting outcomes have been proposed. This review focuses on the correlation of currently utilized assays for outcome, together with the technical and theoretical limitations, to distill current thinking. RECENT FINDINGS: Results demonstrate that C1q status is significantly correlated with AMR and graft loss...
July 18, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28719024/the-immunoproteasome-an-old-player-with-a-novel-and-emerging-role-in-alloimmunity
#9
S K Eskandari, M A J Seelen, G Lin, J R Azzi
Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#10
Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom, Thurid Ahlenstiel-Grunow, Lars Pape
BACKGROUND: Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. METHODS: Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28708813/application-and-interpretation-of-histocompatibility-data-in-liver-transplantation
#11
Russell N Wesson, Eric W Etchill, Jacqueline Garonzik-Wang
PURPOSE OF REVIEW: There has been a resurgence of interest in histocompatibility as it applies to liver transplantation. The association of persistent and de-novo donor specific antibody (DSA) and outcomes after liver transplantation continues to be investigated. RECENT FINDINGS: Consensus continues to evolve regarding the existence of acute and chronic antibody-mediated rejection (AMR) and pathogenicity of DSA and associated pathologic findings after liver transplantation...
July 13, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28707278/daclizumab-development-clinical-trials-and-practical-aspects-of-use-in-multiple-sclerosis
#12
REVIEW
Laura E Baldassari, John W Rose
Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte activation and upregulation of CD56-bright natural killer cells. Intravenous daclizumab (Zenapax™) was initially approved for prevention of rejection in renal transplant. In subsequent early testing, followed by larger-scale phase II and phase III trials, both intravenous and subcutaneous daclizumab have demonstrated clinical efficacy in the treatment of multiple sclerosis...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28701473/zbtb7a-induction-in-alveolar-macrophages-is-implicated-in-anti-hla-mediated-lung-allograft-rejection
#13
Deepak K Nayak, Fangyu Zhou, Min Xu, Jing Huang, Moriya Tsuji, Jinsheng Yu, Ramsey Hachem, Andrew E Gelman, Ross M Bremner, Michael A Smith, Thalachallour Mohanakumar
Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28698834/biomarkers-in-renal-transplantation-an-updated-review
#14
REVIEW
Maurizio Salvadori, Aris Tsalouchos
Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasive indicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment...
June 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28682798/accommodation-and-related-conditions-in-vascularized-composite-allografts
#15
Jeffrey L Platt, Christina L Kaufman, Mayara Garcia de Mattos Barbosa, Marilia Cascalho
PURPOSE OF REVIEW: The outcome of vascularized composite allografts (VCA) often appear unrelated to the presence of donor-specific antibodies (DSA) in blood of the recipient or deposition of complement in the graft. The attenuation of injury and the absence of rejection in other types of grafts despite manifest donor-specific immunity have been explained by accommodation (acquired resistance to immune-mediated injury), adaptation (loss of graft antigen) and/or enhancement (antibody-mediated antigen blockade)...
July 5, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28680827/clinical-analysis-of-single-filtration-plasmapheresis-using-continuous-renal-replacement-therapy-machines-in-kidney-transplantation
#16
Eunsoo Lim, Yujeong Kim, Jong Cheol Jeong, Inwhee Park, Heungsoo Kim, Su Hyung Lee, Chang-Kwon Oh, Gyu-Tae Shin
BACKGROUND: Plasmapheresis has become an essential element of kidney transplantation (KT). In the present study, we report clinical outcomes of filtration plasmapheresis using continuous renal replacement therapy machines with a single filter for the first time in Korea. METHODS: We retrospectively analyzed six patients who underwent filtration plasmapheresis for KT in our center; plasmapheresis was performed using the Plasmaflex (Baxter(®)) with a TPE 2000 filter set (Baxter(®)) in our hemodialysis unit...
June 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28679959/longitudinal-immunological-characterization-of-the-first-presensitized-recipient-of-a-face-transplant
#17
Thet Su Win, Naoka Murakami, Thiago J Borges, Anil Chandraker, George Murphy, Christine Lian, Victor Barrera, Shannan Ho Sui, David Schoenfeld, Jessica Teague, Ericka Bueno, Stefan G Tullius, Bohdan Pomahac, Rachael A Clark, Leonardo V Riella
Rejection affects greater than 80% of face transplants, yet no diagnostic criteria for antibody-mediated rejection (AMR) following face transplantation have been established. Given that different treatment strategies are required to address AMR and T cell-mediated rejection (TCMR), there is a critical need to delineate the features that can differentiate these two alloimmune responses. Here, we report the longitudinal immunological examination of what we believe to be the first and only highly sensitized recipient of a crossmatch-positive face transplant up to 4 years following transplantation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#18
REVIEW
Marieke van der Zwan, Carla C Baan, Teun van Gelder, Dennis A Hesselink
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials...
July 1, 2017: Clinical Pharmacokinetics
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
#19
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
#20
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
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