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Chronic antibody rejection

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https://www.readbyqxmd.com/read/28933341/c4d-expressing-glomerulopathy-and-proteinuria-post-transplantation-of-a-%C3%A2-too-big-for-size-mismatched-kidney-allograft-an-unusual-case-with-good-outcome%C3%A2
#1
Francois Gougeon, Alexei V Mikhailov, Keisha Gibson, Tomasz Kozlowski, Harsharan K Singh, Volker Nickeleit
A 5-year-old severely growth-retarded child with tubulointerstitial, oliguric end-stage renal disease received an adult-size kidney transplant. Three years post grafting under standard triple immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) de novo nephrotic range proteinuria without the nephrotic syndrome developed. Graft function was normal (serum creatinine: 0.2 - 0.3 mg/dL), there were no donor-specific HLA antibodies (DSA), and the urine sediment was inactive. Two biopsies collected 3 and 4 years post-transplantation showed severe glomerular capillary wall remodeling and associated pseudolinear C4d staining as morphologic correlates for the proteinuria...
September 21, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28926189/environmental-peer-pressure-cd4-t-cell-help-in-tolerance-and-transplantation
#2
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/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#3
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/28911876/immunoglobulin-isotype-switching-of-antibodies-to-vimentin-is-associated-with-development-of-transplant-glomerulopathy-following-human-renal-transplantation
#4
Muthukumar Gunasekaran, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, Jason Wellen, T Mohanakumar
BACKGROUND: Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development...
September 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28906028/graft-outcomes-following-diagnosis-of-posttransplant-lymphoproliferative-disease-in-pediatric-kidney-recipients-a-retrospective-study
#5
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/28894792/influence-of-hla-matching-on-the-efficacy-of-allogeneic-mesenchymal-stromal-cell-therapies-for-osteoarthritis-and-degenerative-disc-disease
#6
Javier García-Sancho, Ana Sánchez, Aurelio Vega, David C Noriega, Mercedes Nocito
BACKGROUND: The necessity for more effective therapies for chronic osteoarticular diseases has led to the development of treatments based on mesenchymal stem cells (MSCs), the natural precursors of musculoskeletal tissue. Treatments with autologous MSCs yielded excellent results, with nearly 70% improvement of pain and disability in osteoarthritis and degenerative disc disease. Using allogeneic MSCs is logistically more convenient and would widen the pool of eligible patients, but potential immune rejection should be considered...
September 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28894081/eculizumab-in-renal-transplantation-a-2017-update
#7
Ryszard Grenda, Magdalena Durlik
Despite ongoing progress in renal transplantation, there are still emerging challenges in this field, including consequences of ischemia-reperfusion injury (IRI), pre-existing and produced de novo anti-HLA donor-specific antibodies (DSA), and acute/chronic humoral rejection (AMR), as well as the recurrence of atypical hemolytic-uremic syndrome (aHUS) in genetically predisposed patients. All these conditions are related to the prominent role of the complement system and are deleterious to the fate of the renal graft...
September 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28865128/mechanisms-underlying-human-genetic-diversity-consequence-for-anti-graft-antibody-responses
#8
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/28838437/urgent-lung-transplantation-in-severe-acute-respiratory-failure-based-on-rapidly-progressive-interstitial-lung-disease-a-case-report
#9
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/28794296/recurrent-aa-amyloidosis-combined-with-chronic-active-antibody-mediated-rejection-after-kidney-transplantation
#10
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
https://www.readbyqxmd.com/read/28782692/deleterious-impact-of-c3d-binding-donor-specific-anti-hla-antibodies-after-pediatric-liver-transplantation
#11
Eduardo Couchonnal, Christine Rivet, Stéphanie Ducreux, Jérôme Dumortier, Alexie Bosch, Olivier Boillot, Sophie Collardeau-Frachon, Rémi Dubois, Valérie Hervieu, Patrice André, Jean-Yves Scoazec, Alain Lachaux, Valérie Dubois, Olivier Guillaud
BACKGROUND: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population. METHODS: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate...
August 3, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28776960/role-of-de-novo-donor-specific-anti-hla-antibodies-in-kidney-graft-failure-a-case-control-study
#12
A Castro, J Malheiro, S Tafulo, L Dias, L S Martins, I Fonseca, I Beirão, A Castro-Henriques, A Cabrita
The role of de novo donor-specific anti-human leukocyte antigen (anti-HLA) antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002 and 2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy...
August 4, 2017: HLA
https://www.readbyqxmd.com/read/28775248/clinical-outcome-of-rituximab-and-intravenous-immunoglobulin-combination-therapy-in-kidney-transplant-recipients-with-chronic-active-antibody-mediated-rejection
#13
Tae Hyun Ban, Ji Hyun Yu, Byung Ha Chung, Bum Soon Choi, Cheol Whee Park, Yong-Soo Kim, Chul Woo Yang
BACKGROUND We previously reported that rituximab (RIT) and intravenous immunoglobulin (IVIg) combination therapy is effective in deterring the progression of chronic active antibody-mediated rejection (CAMR), but that report was based on the assessment of a small number of cases for a short period. MATERIAL AND METHODS Forty-three patients with CAMR were recruited during the study period after 2010. The patients were divided into high (n=17, 39.5%) and low proteinuria groups (n=26, 60.5%) based on spot urine protein-to-creatinine ratio of > or <3...
August 4, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28742936/benefits-and-limitations-of-belatacept-in-4-hand-transplanted-patients
#14
J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (CTLA4Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor specific antibodies (DSA) make it an interesting agent in hand transplantation. In order to reduce CNI immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand transplanted patients at month 4, at 6, 9, and 13 years after hand/forearm transplantation. Patients received 5mg/kg belatacept every 2 weeks, the dosing interval was extended to 4 weeks after 5 applications...
July 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#15
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/28717935/rabbit-anti-human-thymocyte-immunoglobulin-for-the-rescue-treatment-of-chronic-antibody-mediated-rejection-after-pediatric-kidney-transplantation
#16
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
#17
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/28701473/zbtb7a-induction-in-alveolar-macrophages-is-implicated-in-anti-hla-mediated-lung-allograft-rejection
#18
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
#19
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
#20
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)...
October 2017: Current Opinion in Organ Transplantation
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