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Chronic antibody rejection

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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
#1
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 (500mg)...
June 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#12
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28506366/antibody-mediated-rejection-after-liver-transplant
#13
REVIEW
Michael Lee
Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy compared with its allograft cohorts of the kidney and lung. Acute AMR is diagnosed based on specific clinical and histopathologic criteria: serum donor specific antibodies, C4d staining, histopathologic findings on liver biopsy, and exclusion of other entities. In contrast, the histologic features of chronic AMR are not as specific and it is a more challenging diagnosis to make. Treatments of acute and chronic AMR include some combination of steroids, immune-modulating agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28489277/pancreas-after-islet-transplantation-in-nonuremic-type-1-diabetes-a-strategy-for-restoring-durable-insulin-independence
#14
S A Wisel, J M Gardner, G R Roll, J Harbell, C E Freise, S Feng, S M Kang, R Hirose, D B Kaufman, A M Posselt, P G Stock
Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28477373/uric-acid-increases-cellular-and-humoral-alloimmunity-in-primary-human-peripheral-blood-mononuclear-cells
#15
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
BACKGROUND: Hyperuricemia is common among kidney transplant recipients and has been associated with worse graft outcome. Since episodes of acute cellular rejection and chronic humoral rejection contribute to decreased graft survival, in this study the effect of uric acid on cellular and humoral alloimmunity was evaluated. METHODS: Cellular alloimmunity was assessed by cell proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC)...
May 5, 2017: Nephrology
https://www.readbyqxmd.com/read/28477360/impact-of-transplant-accessibility-for-sensitized-patients-by-avoiding-unacceptable-antigens
#16
Arnaud Del Bello, Nicolas Congy-Jolivet, Benoit Audry, Corinne Antoine, Laure Esposito, Anne-Laure Hebral, Nassim Kamar
Recent data have confirmed the negative impact of preformed donor-specific antibodies (pDSAs) after liver transplantation (LT). In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in LT recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding pDSAs according to several mean fluorescence intensity (MFI) titer thresholds that have been previously reported to be relevant in LT. Among the 484 included LT candidates, 99 (20...
July 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28465534/low-proportion-of-follicular-regulatory-t-cell-in-renal-transplant-patients-with-chronic-antibody-mediated-rejection
#17
Wen Chen, Jian Bai, Haiyan Huang, Lili Bi, Xiangrui Kong, Yu Gao, Yong Han, Li Xiao, Bingyi Shi
Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465118/development-and-validation-of-a-major-adverse-transplant-event-mate-score-to-predict-late-graft-loss-in-pediatric-heart-transplantation
#18
Christopher S Almond, Helena Hoen, Joseph W Rossano, Chesney Castleberry, Scott R Auerbach, Lingyao Yang, Ashwin K Lal, Melanie D Everitt, Matthew Fenton, Seth A Hollander, Elfriede Pahl, Elizabeth Pruitt, David N Rosenthal, Doff B McElhinney, Kevin P Daly, Manisha Desai
BACKGROUND: There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT. METHODS: Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT...
March 24, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28460546/an-update-on-chemical-pharmacotherapy-options-for-the-prevention-of-kidney-transplant-rejection-with-a-focus-on-costimulation-blockade
#19
Florian Kälble, Matthias Schaier, Sebastian Schäfer, Caner Süsal, Martin Zeier, Claudia Sommerer, Christian Morath
The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28457402/early-vascular-thrombosis-after-kidney-transplantation-can-we-predict-patients-at-risk
#20
R A P de Freitas, M L de Lima, M Mazzali
BACKGROUND: Renal transplant is the therapy of choice for patients with chronic renal disease. In recent years, improvement in immunosuppressive drugs reduced early graft loss associated with acute rejection. However, vascular thrombosis, accounting for 5% of early graft loss, can sensitize the recipient for human leukocyte antibodies, reducing the chance for a second transplant. The aim of this study was to identify risk factors for vascular thrombosis in a single transplant center, to design specific prevention protocol...
May 2017: Transplantation Proceedings
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