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Chronic antibody rejection

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https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#7
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
#8
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/28647211/tubuloreticular-inclusions-in-peritubular-capillaries-of-renal-allografts
#9
Jee Youn Lee, Seung Hwan Song, Yu Seun Kim, Beom Jin Lim, Soon Il Kim, Myoung Soo Kim, Hyeon Joo Jeong
BACKGROUND: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. METHODS: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28640458/long-term-graft-survival-in-patients-with-chronic-antibody-mediated-rejection-with-persistent-peritubular-capillaritis-treated-with-intravenous-immunoglobulin-and-rituximab
#10
William R Mulley, Louis L Huang, Sharmila Ramessur Chandran, Anthony Longano, Liv A R Amos, Kevan R Polkinghorne, David J Nikolic-Paterson, John Kanellis
Chronic antibody-mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor-specific antibody-positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500 mg)...
June 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#11
Theodoros Eleftheriadis, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Triggered by the successful administration of the proteasome inhibitor bortezomib in kidney transplant recipients with acute or chronic antibody-mediated rejection, we evaluated the effect of the proteasome inhibitor CEP-18770 and of the selective immunoproteasome inhibitor ONX-0914 on cellular and humoral alloimmunity. Cellular alloimmunity was assessed by cell proliferation in a two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method, where humoral alloimmunity was induced in one-way MLR...
June 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#12
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed anergy, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28605575/bullous-pemphigoid-and-chronic-kidney-graft-rejection
#13
F Rosique López, A Martínez Losa, P Sánchez-Pedreño Guillén, N Ishii, T Hashimoto, P Martínez García
Bullous pemphigoid (BP) is a disease caused by antibodies against components of the basement membrane, mainly two proteins: BP180 and BP230. We present two cases of BP related to chronic renal rejection. This article is protected by copyright. All rights reserved.
June 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28589364/how-to-simulate-a-germinal-center
#14
Philippe A Robert, Ananya Rastogi, Sebastian C Binder, Michael Meyer-Hermann
Germinal centers host a mini-evolutionary environment where B cells can mutate their receptor and be selected depending on its affinity to target antigens in a process called affinity maturation. Starting from founder cells with a weak B cell receptor affinity, germinal centers release output cells as antibody-secreting cells or memory cells with a very high affinity, a property which is essential for pathogen clearance and immune memory. Therapeutic interventions on the germinal centers are tantalizing approaches to improve vaccines or to support rejection of chronic pathogens such as HIV...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28583516/metabolomics-study-for-identification-of-potential-biomarkers-of-long-term-survival-in-kidney-transplantation-recipients
#15
S-K Lee, B K Kim, H-Y Jung, J-H Cho, S-H Park, Y-L Kim, S-Y Kim, Y-R Yoon, B H Chung, S-H Lee, C-D Kim
BACKGROUND: The recent progress and appropriate use of immunosuppressive drugs have considerably improved the short-term survival in kidney transplantation recipients (KTRs). The development of new strategies to improve long-term survival outcome after kidney transplantation is also becoming important. Although current diagnosis of allograft dysfunction relies on serum creatinine concentration and biopsy, they are nonspecific indicators of allograft function. Therefore, noninvasive, sensitive, and specific biomarkers for the prediction of long-term survival are needed...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28571148/de-novo-focal-segmental-glomerulosclerosis-in-renal-allograft-histological-presentation-and-clinical-correlation-single-centre-experience
#16
Rashmi D Patel, Aruna V Vanikar, Lovelesh A Nigam, Kamal V Kanodia, Kamlesh S Suthar, Himanshu V Patel
INTRODUCTION: Recurrent or de novo glomerulonephritis are one of the well-known causes for renal allograft dysfunction in early and late period after renal transplantation. Focal Segmental Glomerulosclerosis (FSGS) is a devastating lesion of the renal allograft. De novo FSGS is uncommon compared to recurrent FSGS. AIM: To find out the incidence of de novo FSGS. MATERIALS AND METHODS: A retrospective evaluation of renal allograft biopsies was performed from 2007 to 2015, by light microscopy and immunohistochemistry including patient-donor demographics...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28567040/a-unique-cellular-and-molecular-microenvironment-is-present-in-tertiary-lymphoid-organs-of-patients-with-spontaneous-prostate-cancer-regression
#17
María de la Luz García-Hernández, Norma Ofelia Uribe-Uribe, Ricardo Espinosa-González, W Martin Kast, Shabaana A Khader, Javier Rangel-Moreno
OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28565830/correlation-between-pkb-akt-gsk-3%C3%AE-expression-and-tubular-epithelial-mesenchymal-transition-in-renal-allografts-with-chronic-active-antibody-mediated-rejection
#18
Qiang Yan, Hao Luo, Baoyao Wang, Weiguo Sui, Guimian Zou, Huaizhou Chen, Hequn Zou
Chronic antibody-mediated rejection (ABMR) is a major cause of the transplant renal interstitial fibrosis and transplanted kidney epithelial cell transdifferentiation is one of the main mechanisms. The transforming growth factor (TGF)-β1/integrin-linked kinase (ILK) signaling pathway has a significant role in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells; however, the molecular mechanisms of this process have remained elusive. The present study confirmed that Akt and glycogen synthase kinase (GSK)-3β, as TGF-β1 downstream signaling factors, are involved in fibrotic processes caused by kidney disease, which, however, has been rarely reported in the kidney transplant field...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28535528/chronic-allograft-injury-an-overview-of-pathogenesis-and-treatment-strategies
#19
Hector M Madariaga, Leonardo V Riella
Chronic allograft injury (CAI) remains one of the biggest challenges in transplantation as it directly affects the long-term allograft survival, an area in which the scientific and transplantation communities have struggled to improve outcomes. Therefore, understanding the mechanisms of CAI is paramount to implement preventive measures and novel therapeutic options. In this review, we will address the latest evidence on CAI, potential etiologies and risk factors including non-adherence, antibody-mediated rejection, recurrence of glomerular disease, BK nephropathy, and calcineurin nephrotoxicity...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#20
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
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