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Chronic antibody rejection

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https://www.readbyqxmd.com/read/28092129/bortezomib-in-the-treatment-of-antibody-mediated-rejection-in-pediatric-kidney-transplant-recipients-a-multicenter-midwest-pediatric-nephrology-consortium-study
#1
Sarah Kizilbash, Donna Claes, Isa Ashoor, Ashton Chen, Sara Jandeska, Raed Bou Matar, Jason Misurac, Joseph Sherbotie, Katherine Twombley, Priya Verghese
Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients...
January 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#2
Rachel Hogen, Joseph DiNorcia, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress...
January 3, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#3
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#4
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/28009780/kidney-transplant-with-low-levels-of-dsa-or-low-positive-b-flow-crossmatch-an-underappreciated-option-for-highly-sensitized-transplant-candidates
#5
Carrie Schinstock, Manish Gandhi, Wisit Cheungpasitporn, Donald Mitema, Mikel Prieto, Patrick Dean, Lynn Cornell, Fernando Cosio, Mark Stegall
BACKGROUND: Avoiding donor specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed. METHODS: We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low+XM, +DSA/high+XM, and -DSA/+XM and followed for a mean of 4.1±1...
December 22, 2016: Transplantation
https://www.readbyqxmd.com/read/28005572/polyreactive-natural-antibodies-in-transplantation
#6
Emmanuel Zorn, Sarah B See
PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27995324/hla-epitope-matching-in-pediatric-renal-transplantation
#7
Matthew P Sypek, Peter Hughes, Joshua Y Kausman
Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications...
December 19, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27988211/graft-dysfunction-in-chronic-antibody-mediated-rejection-correlates-with-b-cell-dependent-indirect-antidonor-alloresponses-and-autocrine-regulation-of-interferon-%C3%AE-production-by-th1-cells
#8
Kin Yee Shiu, Laura McLaughlin, Irene Rebollo-Mesa, Jingyue Zhao, Hannah Burton, Harriet Douthwaite, Hannah Wilkinson, Vikki Semik, Philippa C Dodd, Paul Brookes, Robert I Lechler, Maria P Hernandez-Fuentes, Claudia Kemper, Anthony Dorling
Chronic antibody-mediated rejection, a common cause of renal transplant failure, has a variable clinical phenotype. Understanding why some with chronic antibody-mediated rejection progress slowly may help develop more effective therapies. B lymphocytes act as antigen-presenting cells for in vitro indirect antidonor interferon-γ production in chronic antibody-mediated rejection, but many patients retain the ability to regulate these responses. Here we test whether particular patterns of T and B cell antidonor response associate with the variability of graft dysfunction in chronic antibody-mediated rejection...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27932144/inhibition-of-jak3-and-pkc-via-immunosuppressive-drugs-tofacitinib-and-sotrastaurin-inhibits-proliferation-of-human-b-lymphocytes-in%C3%A2-vitro
#9
M N Martina, M J Ramirez Bajo, E Bañon-Maneus, D Moya Rull, N Hierro-Garcia, I Revuelta, J M Campistol, J Rovira, F Diekmann
BACKGROUND: Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. METHODS: Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932115/relationship-between-albuminuria-during-the-first-year-and-antibody-mediated-rejection-in-protocol-biopsies-in-kidney-transplant-recipients
#10
L Belmar Vega, E Rodrigo Calabia, J J Gómez Román, J C Ruiz San Millán, L Martín Penagos, M Arias Rodríguez
BACKGROUND: Antibody-mediated rejection is the main cause of deterioration of kidney transplants and frequently is detected only by means of protocol biopsies. The aim of this study was to relate the presence of albuminuria throughout the 1st year to the histologic findings detected by 1-year protocol biopsies in kidney graft recipients. METHODS: Retrospective observational study of 86 protocol biopsies 1 year after transplantation. Albuminuria was measured at 3, 6, 9, and 12 months in urine samples and expressed as albumin/creatinine (mg/g)...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932105/b-cell-activating-factor-levels-are-associated-with-antibody-mediated-histological-damage-in-kidney-transplantation
#11
C Sango, D Merino, D San Segundo, E Rodrigo, M Lopez-Hoyos, A Benito, M Ángeles Ramos, J Gómez-Román, M Arias
INTRODUCTION: Along with death engraftment, in recent years, antibody-mediated damage has been identified as the leading cause of loss of kidney transplants. Despite the recognition of the role of the B-lymphocyte subpopulation in the development of both tolerance and rejection, little is known about the trigger mechanisms and effectors of this humoral response. BACKGROUND: We analyzed the relationship between B lymphocyte subpopulations and levels of B-cell-activating factor (BAFF) with the histological findings in biopsies of renal transplantation...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#12
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909648/fc%C3%AE-receptors-in-solid-organ-transplantation
#13
REVIEW
Tomas Castro-Dopico, Menna R Clatworthy
In the current era, one of the major factors limiting graft survival is chronic antibody-mediated rejection (ABMR), whilst patient survival is impacted by the effects of immunosuppression on susceptibility to infection, malignancy and atherosclerosis. IgG antibodies play a role in all of these processes, and many of their cellular effects are mediated by Fc gamma receptors (FcγRs). These surface receptors are expressed by most immune cells, including B cells, natural killer cells, dendritic cells and macrophages...
2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/27898462/recent-advances-in-allograft-vasculopathy
#14
Jonathan Merola, Daniel D Jane-Wit, Jordan S Pober
PURPOSE OF REVIEW: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. RECENT FINDINGS: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA)...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27893614/the-presence-of-pretransplant-hla-antibodies-does-not-impact-the-development-of-chronic-lung-allograft-dysfunction-or-clad-related-death
#15
Oscar E Zazueta, Sara E Preston, Anna Moniodis, Sabrina Fried, Miae Kim, Keri Townsend, Isabelle Wood, Steve Boukedes, Indira Guleria, Phillip Camp, Souheil El-Chemaly, Ivan O Rosas, Anil Chandraker, Edgar Milford, Hilary J Goldberg
BACKGROUND: Development of Donor-specific Antibodies (DSA) after lung transplantation is associated with antibody mediated rejection (AMR), acute cellular rejection, and bronchiolitis obliterans syndrome (BOS); however, the significance of circulating antibodies before transplant remains unclear. METHODS: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012.We assessed the impact of circulating human leukocyte (HLA) and noncytotoxic Donor Specific antibodies (DSA) detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD related death...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27873464/hyalinosis-lesions-in-renal-transplant-biopsies-time-dependent-complexity-of-interpretation
#16
Gunilla Einecke, Jeff Reeve, Philip F Halloran
Because calcineurin inhibitor immunosuppressive drugs (CNIs) induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years post-transplant. Prevalence of ah lesions increased with time post-transplant (TxBx). Ah-scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging...
November 22, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862883/the-banff-2015-kidney-meeting-report-current-challenges-in-rejection-classification-and-prospects-for-adopting-molecular-pathology
#17
A Loupy, M Haas, K Solez, L Racusen, D Glotz, D Seron, B J Nankivell, R B Colvin, M Afrouzian, E Akalin, N Alachkar, S Bagnasco, J U Becker, L Cornell, C Drachenberg, D Dragun, H de Kort, I W Gibson, E S Kraus, C Lefaucheur, C Legendre, H Liapis, T Muthukumar, V Nickeleit, B Orandi, W Park, M Rabant, P Randhawa, E F Reed, C Roufosse, S V Seshan, B Sis, H K Singh, C Schinstock, A Tambur, A Zeevi, M Mengel
The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies...
January 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27858192/rethinking-peritubular-capillary-basement-membrane-multilayering-in-renal-transplant-pathology-a-case-report
#18
Diana Maria Lopategui, Evelyne Lerut, Maarten Naesens, Rita Van Damme-Lombaerts, Elena Levtchenko, Noël Knops
BACKGROUND: Severe multilayering (ML) of the peritubular capillary basement membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML. METHODS: The patient received a kidney from his mother, whose donor screening was unremarkable...
November 17, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27848058/current-pathological-perspectives-on-chronic-rejection-in-renal-allografts
#19
REVIEW
Shigeo Hara
Chronic rejection in renal transplantation clinically manifests as slow deterioration in allograft function and is a major contributor of late renal graft loss. Most cases of chronic rejection involve chronic antibody-mediated rejection (ABMR) triggered by the interaction of donor-specific alloantibodies with endothelial cells of the microcirculation. The evolution of the Banff classification involved a major revision of the ABMR criteria during the 2000s and led to the inclusion of detailed pathological characteristics of chronic ABMR in the 2013 Banff scheme, including microcirculation damage observed as newly formed basement membranes and arterial fibrous intimal proliferation...
November 16, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27819763/diagnosis-of-acute-cellular-rejection-and-antibody-mediated-rejection-on-lung-transplant-biopsies-a-perspective-from-members-of-the-pulmonary-pathology-society
#20
Anja C Roden, Dara L Aisner, Timothy C Allen, Marie Christine Aubry, Roberto J Barrios, Mary B Beasley, Philip T Cagle, Vera L Capelozzi, Sanja Dacic, Yimin Ge, Lida P Hariri, Sylvie Lantuejoul, Ross A Miller, Mari Mino-Kenudson, Andre L Moreira, Kirtee Raparia, Natasha Rekhtman, Lynette Sholl, Maxwell L Smith, Ming S Tsao, Marina Vivero, Yasushi Yatabe, Eunhee S Yi
CONTEXT: - The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR...
November 7, 2016: Archives of Pathology & Laboratory Medicine
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