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Antibody mediated rejection

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https://www.readbyqxmd.com/read/28938311/feasibility-of-monotherapy-by-rituximab-without-additional-desensitization-in-abo-incompatible-living-donor-liver-transplantation
#1
Hidekazu Yamamoto, Koshi Uchida, Seiichi Kawabata, Kaori Isono, Kohei Miura, Shintaro Hayashida, Yuki Oya, Yasuhiko Sugawara, Yukihiro Inomata
BACKGROUND: Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living donor liver transplantation (ABO-i LT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion therapy (LI) were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT...
September 20, 2017: Transplantation
https://www.readbyqxmd.com/read/28930983/personalized-peptide-arrays-for-detection-of-hla-alloantibodies-in-organ-transplantation
#2
Pan Liu, Tomokazu Souma, Andrew Zu-Sern Wei, Xueying Xie, Xunrong Luo, Jing Jin
In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-HLA immunity, which presents either as pre-existing or de novo generated HLA antibodies that constitute a major transplantation barrier. Current tests are built on a single-antigen beads (SAB) platform using a fixed set of ~100 preselected recombinant HLA antigens to probe transplant sera...
September 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28929636/risk-factors-for-the-development-of-antibody-mediated-rejection-in-highly-sensitized-pediatric-kidney-transplant-recipients
#3
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/28926521/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
#4
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. 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...
October 2017: Transplantation
https://www.readbyqxmd.com/read/28926189/environmental-peer-pressure-cd4-t-cell-help-in-tolerance-and-transplantation
#5
REVIEW
Dana Tedesco, Arash Grakoui
The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co-transplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance...
September 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28923620/late-conversion-to-belatacept-after-kidney-transplantation-outcome-and-prognostic-factors
#6
M Dürr, N Lachmann, B Zukunft, D Schmidt, K Budde, S Brakemeier
BACKGROUND: Conversion to belatacept at a later point after kidney transplantation (KT) as a rescue therapy has been shown to be beneficiary in an increasing number of patients, but prognostic factors for a favorable outcome have never been investigated. METHODS: The present study analyzed all KT patients after late conversion to belatacept in a single center regarding graft survival and changes in estimated glomerular filtration rate (eGFR), proteinuria, and mean fluorescence intensity (MFI) of donor-specific antibodies (DSA)...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921709/kidney-allograft-failure-in-the-steroid-free-immunosuppression-era-a-matched-case-control-study
#7
Mohamad M Alkadi, Jim Kim, Meredith J Aull, Joseph E Schwartz, John R Lee, Anthony Watkins, Jun B Lee, Darshana M Dadhania, Surya V Seshan, David Serur, Sandip Kapur, Manikkam Suthanthiran, Choli Hartono, Thangamani Muthukumar
We studied the causes and predictors of death-censored kidney allograft failure among 1670 kidney recipients transplanted at our center in the corticosteroid-free maintenance immunosuppression era. As of January 1, 2012, we identified 137 recipients with allograft failure; 130 of them (cases) were matched 1-1 for recipient age, calendar year of transplant and donor type with 130 recipients with functioning grafts (controls). Median time to allograft failure was 29 months (interquartile range 18-51). Physician validated and biopsy confirmed categories of allograft failure were: acute rejection (21%), glomerular disease (19%), transplant glomerulopathy (13%), interstitial fibrosis tubular atrophy (10%), and polyomavirus-associated nephropathy (7%)...
September 18, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#8
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28906028/graft-outcomes-following-diagnosis-of-posttransplant-lymphoproliferative-disease-in-pediatric-kidney-recipients-a-retrospective-study
#9
Nele K Kanzelmeyer, Britta Maecker-Kolhoff, Henriette Zierhut, Christian Lerch, Murielle Verboom, Dieter Haffner, Lars Pape
Data related to graft outcomes following posttransplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (8 boys) for three years after diagnosis of PTLD, with a loss of follow-up after 2 years in 2/12. In all cases, intensity of immunosuppressive therapy was reduced, with switch from calcineurin inhibitor to a mammalian target of rapamcyin (mTOR) inhibitor in 6 cases. Nine children were treated with 6 doses of rituximab according to the PED-PTLD-2005 protocol, with additional treatment in one child as per protocol...
September 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28882429/natural-killer-cells-unleashed-checkpoint-receptor-blockade-and-bike-trike-utilization-in-nk-mediated-anti-tumor-immunotherapy
#10
REVIEW
Zachary B Davis, Daniel A Vallera, Jeffrey S Miller, Martin Felices
Natural killer (NK) cells have long been known to mediate anti-tumor responses without prior sensitization or recognition of specific tumor antigens. However, the tumor microenvironment can suppress NK cell function resulting in tumor escape and disease progression. Despite recent advances in cytokine therapy and NK cell adoptive transfer, tumor expression of ligands to NK - expressed checkpoint receptors can still suppress NK mediated tumor lysis. This review will explore many of the checkpoint receptors tumors utilize to manipulate the NK cell response as well as some of the current and upcoming pharmacological solutions to limit tumor suppression of NK cell function...
September 4, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#11
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/28867309/b-cell-activating-factor-baff-reflects-patients-immunological-risk-profile-after-kidney-transplantation
#12
A Schuster, B Jung, J Hofbauer, L Kühne, D Zecher, B Banas, T Bergler
The B-cell activating factor BAFF plays an important role in the development and maturation of B-lymphocytes, which can contribute to the generation of donor-specific antibodies and thus may influence graft function and graft survival. Inconsistent data on the role of BAFF levels after renal transplantation for the formation of donor-specific antibodies and the contribution for allograft rejection exist. The aim of the current study was to determine to what extent the degree of pre-immunization is reflected by each patient's BAFF levels before transplantation and in the follow-up...
August 31, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28865128/mechanisms-underlying-human-genetic-diversity-consequence-for-anti-graft-antibody-responses
#13
REVIEW
Roman Reindl-Schwaighofer, Andreas Heinzel, Lorenzo Signorini, Olivier Thaunat, Rainer Oberbauer
This review focuses on the emerging concept of genome-wide genetic variation as basis of an alloimmune response. Chronic antibody mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor specific alloantibodies is driven by indirect allorecognition of donor derived peptides representing a form of conventional T-cell response...
September 2, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28864337/complement-genomics-and-antibody-mediated-rejection-in-heart-recipients
#14
EDITORIAL
Javier Carbone
In this issue of the Journal of Heart and Lung Transplantation, Marrón-Liñares et al report the results of an interesting study in which they evaluated 51 genes associated with the complement pathway in a small number of heart recipients to explore their relationship with antibody-mediated rejection (AMR). Next-generation sequencing was used in 46 heart transplant recipients (23 with AMR and 23 without AMR). The authors identified a significant association of 2 single-nucleotide polymorphisms with the absence or presence of AMR, respectively, p...
August 19, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28858176/midterm-outcomes-of-12-renal-transplant-recipients-treated-with-eculizumab-to-prevent-atypical-hemolytic-syndrome-recurrence
#15
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/28839122/c1q-test-for-identification-of-sensitized-liver-recipients-at-risk-of-early-acute-antibody-mediated-rejection
#16
Tomasz Kozlowski, Eric T Weimer, Kenneth Andreoni, John Schmitz
BACKGROUND The majority of liver recipients transplanted with positive crossmatch have a post-transplant course free of acute antibody-mediated rejection (AMR). However, 10% of sensitized recipients develop early severe AMR. There is no clear strategy that would allow for predicting the postoperative course in sensitized liver recipients. One of the possible factors contributing to the dichotomous course in sensitized recipients may be the complement-binding characteristics of the donor-specific antibodies (DSA)...
August 25, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28838449/successful-blood-transfusion-management-of-a-living-donor-liver-transplant-recipient-in-the-presence-of-anti-jr-a-a-case-report
#17
N Kurata, Y Onishi, H Kamei, T Hori, M Komagome, C Kato, T Matsushita, Y Ogura
A 48-year-old Japanese woman was diagnosed with Budd-Chiari syndrome and transferred for possible living donor liver transplantation (LDLT). Examinations before LDLT revealed that the recipient had anti-Jr(a) and preformed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA). Rituximab was administrated at 16 days prior to the patient's scheduled LDLT for the prophylaxis of antibody-mediated rejection by DSA. The clinical significance of anti-Jr(a) has not been clearly established because of the rarity of this antibody, so we discussed blood transfusion strategy with the Department of Blood Transfusion Service and prepared for Jr(a)-negative packed red blood cells (RBCs)...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28838437/urgent-lung-transplantation-in-severe-acute-respiratory-failure-based-on-rapidly-progressive-interstitial-lung-disease-a-case-report
#18
I Madurka, J Elek, N Schönauer, T Bartók, K Kormosói-Tóth, É Zöllei, Á Ghimessy, G Lang, W Klepetko, F Rényi-Vámos
Lung transplantation (LUTX) became a worldwide accepted standard therapy for certain well-defined chronic end-stage lung diseases. Until recently, patients on mechanical ventilation or extracorporeal life support techniques were hardly eligible for LUTX because of the inferior short-term results. However, a paradigm shift has occurred, and now these techniques represent bridging options to LUTX for listed patients. In the current practice, transplantation from the intensive care unit (ICU) is not extraordinary in patients on the waiting list...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28833936/persistent-c4d-and-antibody-mediated-rejection-in-pediatric-renal-transplant-patients
#19
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/28794296/recurrent-aa-amyloidosis-combined-with-chronic-active-antibody-mediated-rejection-after-kidney-transplantation
#20
Min-Kyung Yeo, Young Rok Ham, Song-Yi Choi, Yong-Moon Lee, Moon Hyang Park, Kwang-Sun Suh
Kidney transplantation for amyloidosis remains a contentious issue. Recurrence of amyloidosis is one of the risks of transplantation. Chronic active antibody-mediated rejection is an important cause of chronic allograft dysfunction. A 47-year-old woman underwent kidney transplantation due to renal AA amyloidosis with unknown etiology. Six years posttransplantation, a kidney biopsy showed AA amyloidosis with chronic active antibody-mediated rejection. Donor-specific antibody class II was positive. The patient underwent intravenous plasmapheresis and treatment with rituximab and colchicine...
July 2017: Iranian Journal of Kidney Diseases
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