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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/29331505/successful-treatment-of-anti-angiotensin-ii-type-1-receptor-antibody-associated-rejection-in-kidney-transplantation-a-case-report
#1
P Wiwattanathum, A Ingsathit, D Thammanichanond, S Worawichawong
Angiotensin II type 1 receptor (AT1R) antibody, a non-HLA antibody, has been found to have a detrimental effect on kidney allografts. Similarly to HLA antibodies, recipients who have AT1R antibodies are at risk for allograft rejection and poor long-term graft outcome. Besides mediating allograft rejections via direct effects on endothelial and vascular smooth muscle without complement activation, AT1R antibodies may lead to accelerated hypertension via the renin-angiotensin pathway. There has been no definite level of AT1R antibody that predicts allograft rejection...
January 10, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29330111/soluble-major-histocompatibility-complex-class-i-related-chain-a-smica-levels-influence-graft-outcome-following-renal-transplantation
#2
Ajay K Baranwal, Sanjeev Goswami, Deepali K Bhat, Gurvinder Kaur, Sanjay K Agarwal, Narinder K Mehra
BACKGROUND: Since soluble isoforms of MICA play an important role in modulating the immune response, we evaluated a possible correlation between their levels and development of acute rejection following renal transplantation. METHODS: Serum samples collected at pre- and different time points posttransplant from 137 live related donor renal transplant recipients were evaluated retrospectively for sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy volunteers were also tested as controls...
January 9, 2018: Human Immunology
https://www.readbyqxmd.com/read/29327261/chronic-rejection-after-intestinal-transplant-where-are-we-in-order-to-avert-it
#3
REVIEW
Augusto Lauro, Mihai Oltean, Ignazio R Marino
Chronic rejection affects the long-term survival of all solid organ transplants and, among intestinal allografts, occurs in up to 10% of the recipients. The insidious clinical evolution of the chronic allograft enteropathy, the absence of noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No pharmacological approach has been proven effective, and allograft removal nowadays still represents the only available therapy. The inclusion of the liver in the visceral allograft appears to be the only intervention affecting the development of chronic rejection, as revealed by large-center studies and registry reports...
January 11, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29326157/targeting-b-cells-and-plasma-cells-in-glomerular-diseases-translational-perspectives
#4
Eva Schrezenmeier, David Jayne, Thomas Dörner
The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells...
January 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29319615/clinical-and-pathological-features-of-plasma-cell-rich-acute-rejection-after-kidney-transplantation
#5
Jumpei Hasegawa, Kazuho Honda, Kazuya Omoto, Sachiko Wakai, Hiroki Shirakawa, Masayoshi Okumi, Hideki Ishida, Shohei Fuchinoue, Motoshi Hattori, Kazunari Tanabe
BACKGROUND: Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general the prognosis of PCAR is poor, and its clinical and pathological features remain unclear. METHODS: We performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients...
January 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29319177/characterization-of-ectopic-lymphoid-structures-in-different-types-of-acute-renal-allograft-rejection
#6
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29317301/antibody-mediated-rejection-due-to-de-novo-dsa-causing-venous-thrombosis-of-pancreas-allograft-a-case-report
#7
Kunal Yadav, Adrian Cotterell, Pamela Kimball, Laura Warmke, Melissa Contos, Gaurav Gupta, Anne King, Dhiren Kumar, Marlon Levy
This case describes a 34year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection. She later received a pancreas allograft, again with a weakly positive FCXM, without DSA. After good initial graft function, she developed hyperglycemia six weeks posttransplant. Cross-sectional imaging demonstrated non-enhancing pancreas allograft with new vein thrombosis...
January 6, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29316217/exosomes-expressing-the-self-antigens-myosin-and-vimentin-play-an-important-role-in-syngeneic-cardiac-transplant-rejection-induced-by-antibodies-to-cardiac-myosin
#8
Monal Sharma, Wei Liu, Sudhir Perincheri, Muthukumar Gunasekaran, T Mohanakumar
Long-term success of heart transplantation is hindered by humoral and cell-mediated immune responses. We studied preexisting antibodies to two cardiac self-antigens, myosin and vimentin, and exosomes induced by antibodies to self-antigens in eliciting immune responses to cardiac grafts. After syngeneic heterotopic murine heart transplantation, rabbit anti-myosin or normal rabbit immunoglobulin was administered at days 0 or 7. Sera were collected after heartbeat cessation and cellular infiltration was analyzed, and exosomes were isolated from sera...
January 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29315820/de-novo-donor-specific-antibody-following-bk-nephropathy-the-incidence-and-association-with-antibody-mediated-rejection
#9
Wisit Cheungpasitporn, Walter K Kremers, Elizabeth Lorenz, Hatem Amer, Fernando G Cosio, Mark D Stegall, Manish J Gandhi, Carrie A Schinstock
BACKGROUND AND OBJECTIVES: The risk of de novo donor-specific antibody (dnDSA) development following BK viremia (BKV) or nephropathy (BKN) after kidney transplant remains unclear. We aimed to evaluate the relationships among dnDSA, BKV (BK blood PCR >15,000 copies), BKN, antibody mediated rejection (AMR) and allograft loss. PATIENTS AND METHODS: We performed a retrospective cohort study of 904 solitary kidney transplant recipients transplanted between 10/2007 and 5/2014...
January 8, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29315141/the-treatment-of-antibody-mediated-rejection-in-kidney-transplantation-an-updated-systematic-review-and-meta-analysis
#10
Susan S Wan, Tracey D Ying, Kate Wyburn, Darren M Roberts, Melanie Wyld, Steven J Chadban
BACKGROUND: Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B-cells, plasma-cells and the complement system have featured in recent studies of AMR. METHODS: We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE and CENTRAL from inception to February 2017. RESULTS: Of 14,380 citations we identified 21 studies, including 10 randomized controlled trials, involving 751 participants...
January 8, 2018: Transplantation
https://www.readbyqxmd.com/read/29312755/acute-rejection
#11
REVIEW
Mark Benzimra, Greg L Calligaro, Allan R Glanville
Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29300203/evolving-criteria-for-the-diagnosis-of-antibody-mediated-rejection-in-renal-allografts
#12
Mark Haas
PURPOSE OF REVIEW: To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. RECENT FINDINGS: The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR...
January 2, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29298238/desensitization-and-prevention-of-antibody-mediated-rejection-in-vascularized-composite-allotransplantation-by-syngeneic-hematopoietic-stem-cell-transplantation
#13
Howard D Wang, Samuel A J Fidder, Devin T Miller, Georg J Furtmüller, Ali Reza Ahmadi, Felix Nägele, Joseph Lopez, Amy Quan, Joshua Budihardjo, Denver M Lough, Burcu Akpinarli, Joanna Etra, Dalibor Vasilic, Giorgio Raimondi, W P Andrew Lee, Robert A Montgomery, Zhaoli Sun, Gerald Brandacher
BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection (AMR). Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent AMR in VCA. METHODS: Skin transplants from Dark Agouti (DA) to Lewis rats were performed for sensitization...
January 2, 2018: Transplantation
https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#14
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288556/rna-expression-profiling-of-non-human-primate-renal-allograft-rejection-identifies-tolerance
#15
R N Smith, M Matsunami, B A Adam, I A Rosales, T Oura, A B Cosimi, T Kawai, M Mengel, R B Colvin
Tolerance induction to prevent allograft rejection is a long standing clinical goal. However, convincing and dependable tolerance identification remains elusive. Hypothesizing that intragraft RNA expression is informative in both rejection and tolerance, we profile intra-renal allograft RNA expression in a mixed chimerism renal allograft model of Cynomolgus monkeys and identify biologically significant tolerance. Analysis of 67 genes identified three dominant factors, each with a different pattern of gene expressions, relating to T cell mediated rejection (TCMR), chronic antibody mediated rejection (CAMR), or Tolerance...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29288041/global-quality-assessment-of-liver-allograft-c4d-staining-during-acute-antibody-mediated-rejection-in-formalin-fixed-paraffin-embedded-tissue
#16
Neil Dah, Bellamy Co, M Smith, H Haga, Y Zen, M Sebagh, K Ruppert, J Lunz, S G Hübscher, A J Demetris
Discussion of liver antibody mediated rejection during the 2011, 2013 and 2015 Banff liver sessions raised concerns over reliability of complement fragment 4d (C4d) staining, precipitating a global survey followed by a tissue microarray staining quality assessment study among centers on formalin-fixed, paraffin-embedded tissue. Tissue microarray sections containing tissue plugs of resected native and allograft (with acute antibody mediated rejection) liver, heart and kidney (n=33 total cores) were sent to 31 centers for C4d staining using local method (s) and pathologist scoring...
December 26, 2017: Human Pathology
https://www.readbyqxmd.com/read/29277566/pretransplant-serum-baff-levels-are-associated-with-pretransplant-hla-immunization-and-renal-allograft-survival
#17
Justa Friebus-Kardash, Benjamin Wilde, Deniz Keles, Andreas Heinold, Andreas Kribben, Oliver Witzke, Falko Markus Heinemann, Ute Eisenberger
BACKGROUND: The essential function of B cell-activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood. METHODS: Objective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival...
December 22, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/29259604/novel-non-histocompatibility-antigen-mismatched-variants-improve-the-ability-to-predict-antibody-mediated-rejection-risk-in-kidney-transplant
#18
Silvia Pineda, Tara K Sigdel, Jieming Chen, Annette M Jackson, Marina Sirota, Minnie M Sarwal
Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA) mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR), a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA) antigens. AMR is incompletely diagnosed as donor/recipient (D/R) matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29250075/identification-and-characterization-of-neoantigens-as-well-as-respective-immune-responses-in-cancer-patients
#19
REVIEW
Eva Bräunlein, Angela M Krackhardt
Cancer immunotherapy has recently emerged as a powerful tool for the treatment of diverse advanced malignancies. In particular, therapeutic application of immune checkpoint modulators, such as anti-CTLA4 or anti-PD-1/PD-L1 antibodies, have shown efficacy in a broad range of malignant diseases. Although pharmacodynamics of these immune modulators are complex, recent studies strongly support the notion that altered peptide ligands presented on tumor cells representing neoantigens may play an essential role in tumor rejection by T cells activated by anti-CTLA4 and anti-PD-1 antibodies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29246419/hla-epitope-matching-in-kidney-transplantation-an-overview-for-the-general-nephrologist
#20
REVIEW
Matthew Sypek, Joshua Kausman, Steve Holt, Peter Hughes
Rapid changes in tissue-typing technology, including the widespread availability of highly specific molecular typing methods and solid-phase assays for the detection of allele-specific anti-HLA antibodies, make it increasingly challenging to remain up to date with developments in organ matching. Terms such as epitopes and eplets abound in the transplantation literature, but often it can be difficult to see what they might mean for the patient awaiting transplantation. In this review, we provide the historical context for current practice in tissue typing and explore the potential role of HLA epitopes in kidney transplantation...
December 12, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
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