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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/28510327/pre-existing-diabetes-is-a-risk-factor-for-increased-rates-of-cellular-rejection-after-kidney-transplantation-an-observational-cohort-study
#1
S Johal, F Jackson-Spence, H Gillott, S Tahir, J Mytton, F Evison, B Stephenson, J Nath, A Sharif
AIM: To investigate whether people with diabetes have an elevated risk of kidney allograft rejection in a well characterized clinical cohort in the setting of contemporary immunosuppression. METHODS: We conducted a retrospective cohort study including all kidney allograft recipients at a single centre between 2007 and 2015, linking clinical, biochemical and histopathological data from electronic patient records. RESULTS: Data were analysed for 1140 kidney transplant recipients...
May 16, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
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
#2
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
#3
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/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#4
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28497796/potent-antitumour-activity-of-interleukin-2-fc-fusion-proteins-requires-fc-mediated-depletion-of-regulatory-t-cells
#5
Rodrigo Vazquez-Lombardi, Claudia Loetsch, Daniela Zinkl, Jennifer Jackson, Peter Schofield, Elissa K Deenick, Cecile King, Tri Giang Phan, Kylie E Webster, Jonathan Sprent, Daniel Christ
Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8(+) and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25(+) regulatory T-cells (Tregs) and results in strong expansion of CD25(-) cytotoxic subsets...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28496440/fc%C3%AE-chimeric-receptor-engineered-t-cells-methodology-advantages-limitations-and-clinical-relevance
#6
REVIEW
Sara Caratelli, Tommaso Sconocchia, Roberto Arriga, Andrea Coppola, Giulia Lanzilli, Davide Lauro, Adriano Venditti, Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Soldano Ferrone, Giuseppe Sconocchia
For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient's immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient's immune system can recognize and reject his tumor if appropriate strategies are implemented...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28480647/increased-circulating-t-lymphocytes-expressing-hla-dr-in-kidney-transplant-recipients-with-microcirculation-inflammation
#7
Hee Yeon Jung, Yong Jin Kim, Ji Young Choi, Jang Hee Cho, Sun Hee Park, Yong Lim Kim, Hyung Kee Kim, Seung Huh, Dong Il Won, Chan Duck Kim
We consecutively enrolled 82 kidney transplant recipients (KTRs) with stable renal function and 24 KTRs who underwent indication biopsy to compare the histological grading of renal allografts with the activity of circulating T lymphocyte subsets and monocytes determined by flow cytometry, which were obtained at 2 weeks after kidney transplantation (KT) and at the time of indication biopsy, respectively. The sum of the scores of glomerulitis (g) + peritubular capillaritis (ptc), inflammation (i) + tubulitis (t), interstitial fibrosis (ci) + tubular atrophy (ct), and fibrointimal thickening (cv) + arteriolar hyaline thickening (ah) was used to assign a histological grade to the renal allograft samples...
June 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28477373/uric-acid-increases-cellular-and-humoral-alloimmunity-in-primary-human-peripheral-blood-mononuclear-cells
#8
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
#9
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 after liver transplantation. In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in liver-transplant recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding preformed DSAs according to several MFI-titer thresholds that have been previously reported to be relevant in liver transplantation. Among the 484 included LT candidates, 99 (20...
May 6, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28467296/immunohistopathologic-characterization-of-plasma-cell-rich-acute-rejection-in-living-related-renal-transplant-recipients
#10
Muhammed Mubarak, Khawar Abbas, Mirza Naqi Zafar, Tahir Aziz
OBJECTIVES: Our aim was to analyze the immunohistopathologic features of plasma cell-rich acute rejection in a living-related renal transplant setting. MATERIALS AND METHODS: Renal allograft biopsies of 50 cases of plasma cell-rich acute rejection were reviewed, and the main immunohistopathologic features were analyzed. The biopsies were studied using light microscopy, immunofluorescence, and immunohistochemistry and reported according to Banff classification. Biopsy findings were correlated with graft function and outcome...
May 3, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28465534/low-proportion-of-follicular-regulatory-t-cell-in-renal-transplant-patients-with-chronic-antibody-mediated-rejection
#11
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
#12
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
#13
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...
May 9, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28453891/towards-a-better-risk-stratification-for-late-antibody-mediated-rejection-in-abo-incompatible-kidney-recipients
#14
Philippe Grimbert
During the last 25 years, increasing organ shortage enforced the development for living donor programs including ABO-incompatible (ABOi) renal transplantation, paired donor exchange program and transplantation across a positive cross-match. ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantation. This article is protected by copyright. All rights reserved.
April 28, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28452922/chronic-amr-in-liver-transplant-validation-of-the-1-year-camr-score-s-ability-to-determine-long-term-outcome
#15
Jacqueline G O'Leary, Cory Smith, Juncao Cai, Brent Hart, Linda W Jennings, Matthew Everly, Goran B Klintmalm, Anthony J Demetris
BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has recently predicted 50%10-year death censored allograft loss in patients with Donor Specific Alloantibodies (DSA) Mean Florescence Intensity (MFI) >10 000 and requires confirmation in patients with lower MFI (1000-10 000). METHODS: All patients who underwent liver transplantation (LT) from 1/00-4/09, had DSA (MFI ≥1000) in serum 10-14 months post-LT, and had a protocolized liver biopsy were evaluated (n=230)...
April 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28450866/impact-of-non-human-leukocyte-antigen-specific-antibodies-in-kidney-and-heart-transplantation
#16
REVIEW
Xiaohai Zhang, Nancy L Reinsmoen
The presence of donor human leukocyte antigen (HLA)-specific antibodies has been shown to be associated with graft loss and decreased patient survival, but it is not uncommon that donor-specific HLA antibodies are absent in patients with biopsy-proven antibody-mediated rejection. In this review, we focus on the latest findings on antibodies against non-HLA antigens in kidney and heart transplantation. These non-HLA antigens include myosin, vimentin, Kα1 tubulin, collagen, and angiotensin II type 1 receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28449409/real-time-central-assessment-of-kidney-transplant-indication-biopsies-by-microarrays-the-intercomex-study
#17
Philip F Halloran, Jeff Reeve, Enver Akalin, Olivier Aubert, Georg A Bohmig, Daniel Brennan, Jonathan Bromberg, Gunilla Einecke, Farsad Eskandary, Clement Gosset, Jean-Paul Duong Van Huyen, Gaurav Gupta, Carmen Lefaucheur, Andrew Malone, Roslyn B Mannon, Daniel Seron, Joana Sellares, Matthew Weir, Alexandre Loupy
We performed a prospective trial to assess the feasibility of real-time central molecular assessment of kidney transplant biopsies from 10 North American and European centers. Biopsies taken one day to 34 years post-transplant were stabilized in RNAlater, couriered overnight at ambient temperature to the central laboratory, and processed (29 hour workflow) using microarrays to assess T cell-mediated and antibody-mediated rejection (TCMR, ABMR). Of 538 biopsies submitted, 519 (96%) were sufficient for microarray analysis (average length 3mm)...
April 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28447927/unexpected-positive-prospective-crossmatches-in-organ-transplant
#18
REVIEW
Judith Desoutter, Marie-Joelle Apithy, Nicolas Guillaume
Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complement-dependent cytotoxicity assays and/or flow cytometry-based methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28447925/luminex-solid-phase-crossmatch-for-de-novo-donor-specific-antibodies-in-living-donor-related-transplants
#19
Sonia Mehrotra, Raj Kumar Sharma, Mahabaleshwar Mayya, Amit Gupta, Narayan Prasad, Anupma Kaul, Dharmendra Singh Bhadauria
OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121 recipients in our study group, 26 (21...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#20
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
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