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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/28101959/comprehensive-analysis-of-transcript-changes-associated-with-allograft-rejection-combining-universal-and-selective-features
#1
Philip F Halloran, Jeffery M Venner, Konrad S Famulski
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated (TCMR) or antibody-mediated rejection (ABMR). We used eight class comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all non-rejecting biopsies, including other diseases. The universal algorithm, rejection vs...
January 19, 2017: American Journal of Transplantation
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
#2
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/28073833/exosomal-mir-142-3p-is-increased-during-cardiac-allograft-rejection-and-augments-vascular-permeability-through-down-regulation-of-endothelial-rab11fip2-expression
#3
Ihdina Sukma Dewi, Selvi Celik, Anna Karlsson, Zsuzsanna Hollander, Karen Lam, Janet-Wilson McManus, Scott Tebbutt, Raymond Ng, Paul Keown, Robert McMaster, Bruce McManus, Jenny Öhman, Olof Gidlöf
AIMS: Exosome-mediated microRNA transfer is a recently discovered mode of cell-to-cell communication, in which microRNAs act as paracrine molecules, exerting their regulatory effects in recipient cells. T cells and endothelial cells are two main players in the mechanism of acute cellular cardiac rejection. The aim of this study was to investigate the role of exosomal microRNAs in the crosstalk between T cells and endothelial cells and its implications for the molecular mechanisms that drive acute cellular rejection in heart transplantation...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28070711/immune-suppression-during-preclinical-drug-development-mitigates-immunogenicity-mediated-impact-on-therapeutic-exposure
#4
Jonathan Herskovitz, Josiah Ryman, Theingi Thway, Stephanie Lee, Lei Zhou, Narendra Chirmule, Bernd Meibohm, Vibha Jawa
In the clinical setting, anti-drug antibodies (ADA) against biotherapeutics can influence patient safety and interfere with product efficacy. High immunogenicity has been addressed in clinic by concomitant immune suppression, such as co-administration of methotrexate with enzyme replacement therapy (ERT) and combination tacrolimus/sirolimus treatment for prophylaxis against organ transplant rejection. This study investigates the use of such immune suppressants in mitigating ADA responses to a fully human monoclonal antibody (mAb1) in preclinical animal studies...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28062921/targeted-deletion-of-traf2-allows-immunosuppression-free-islet-allograft-survival-in-mice
#5
Jeanette E Villanueva, Stacey N Walters, Mitsuru Saito, Elisabeth K Malle, Nathan W Zammit, Katherine A Watson, Robert Brink, Nicole L La Gruta, Stephen I Alexander, Shane T Grey
AIMS/HYPOTHESIS: Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28061513/angiopoietin-2-blockade-promotes-survival-of-corneal-transplants
#6
Liwei Zhang, Guangyu Li, Roberto Sessa, Gyeong Jin Kang, Meng Shi, Shaokui Ge, Anna Jiang Gong, Ying Wen, Sudhakar Chintharlapalli, Lu Chen
Purpose: Corneal transplantation remains the last hope for vision restoration, and lymphangiogenesis (LG) is a primary mediator of transplant rejection. This study was to investigate the specific role of angiopoietin-2 (Ang-2) in transplantation-associated LG and graft rejection. Methods: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice to assess the effects of Ang-2 blockade via neutralizing antibody...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#7
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
#8
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/28058219/impact-of-preformed-donor-specific-antibodies-against-hla-class-i-on-kidney-graft-outcomes-comparative-analysis-of-exclusively-anti-cw-vs-anti-a-and-or-b-antibodies
#9
Sofia Santos, Jorge Malheiro, Sandra Tafulo, Leonídio Dias, Rute Carmo, Susana Sampaio, Marta Costa, Andreia Campos, Sofia Pedroso, Manuela Almeida, La Salete Martins, Castro Henriques, António Cabrita
AIM: To analyze the clinical impact of preformed antiHLA-Cw vs antiHLA-A and/or -B donor-specific antibodies (DSA) in kidney transplantation. METHODS: Retrospective study, comparing 12 patients transplanted with DSA exclusively antiHLA-Cw with 23 patients with preformed DSA antiHLA-A and/or B. RESULTS: One year after transplantation there were no differences in terms of acute rejection between the two groups (3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1)...
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
#10
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/28009783/treatment-of-acute-antibody-mediated-renal-allograft-rejection-with-cyclophosphamide
#11
Johannes Waiser, Michael Duerr, Klemens Budde, Birgit Rudolph, Kaiyin Wu, Friederike Bachmann, Fabian Halleck, Constanze Schönemann, Nils Lachmann
BACKGROUND: Antibody-mediated rejection (ABMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated, whether cyclophosphamide combined with plasmapheresis (PPH) and intravenous immunoglobulins (IVIG) is an option for patients with ABMR. METHODS: Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute ABMR with i...
December 22, 2016: Transplantation
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
#12
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
#13
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/28002655/optimal-dosage-regimen-for-rituximab-in-abo-incompatible-living-donor-liver-transplantation
#14
Hiroto Egawa, Koji Umeshita, Shinji Uemoto
BACKGROUND: Rituximab has greatly improved the outcomes of ABO-incompatible living donor liver transplantation (ABO-I LDLT). To clarify the optimal regimen for rituximab in adult ABO-I LDLT, a multicenter study was conducted in Japan. METHODS: Clinical data of 33 adult patients undergoing ABO-I LDLT at 15 centers in 2013 were retrospectively corrected. RESULTS: The targeted blood type was A1 in 18, B in 14, and AB in 1 patient. Rituximab was administered at 7 to 48 days before LT, at a dose of 375 mg/m(2) in 12 patients, 500 mg in 15 patients, 300 mg in 5 patients, and 100 mg in 1 patient...
December 21, 2016: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28001189/acute-myeloid-leukemia-after-kidney-transplantation-a-case-report-and-literature-review
#15
Francesca Cardarelli, Vanesa Bijol, Anil Chandraker, Cindy Varga, Leonardo V Riella
The incidence of malignancy is greater in kidney transplant recipients compared to the general population, though the higher risk is not equally distributed to all types of cancers. In face of the increased longevity of renal transplant recipients, certain cancers, such as acute leukemias, are becoming more prevalent. Acute myeloid leukemia (AML) typically presents with cytopenias and infections, both common findings after kidney transplantation. Therefore, the diagnosis of AML may be initially overlooked in these patients...
December 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/28000532/maintenance-immunosuppressants-in-the-management-of-antibody-mediated-renal-allograft-rejection-which-regimen-is-best
#16
Yiqun Zhou, Xiaolan Li, Yun Liu, Qiquan Sun
Antibody-mediated rejection (AMR) is a pivotal cause of long-term graft failure following renal transplantation. De novo donor-specific antibody reduction is essential to prevent AMR and improve long-term graft survival in renal transplant recipients. Although the number of early AMR episodes can be successfully controlled by attenuating de novo donor-specific antibodies, the long-term outcomes are unsatisfactory. Numerous studies have focused on new strategies to reverse AMR, but the available evidence suggests that maintenance immunosuppressive agents play important roles...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27995324/hla-epitope-matching-in-pediatric-renal-transplantation
#17
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/27992962/c1q-binding-is-not-an-independent-risk-factor-for-kidney-allograft-loss-after-an-acute-antibody-mediated-rejection-episode-a-retrospective-cohort-study
#18
Anissa Moktefi, Juliette Parisot, Dominique Desvaux, Florence Canoui-Poitrine, Isabelle Brocheriou, Julie Peltier, Vincent Audard, Tomek Kofman, Caroline Suberbielle, Philippe Lang, Eric Rondeau, Philippe Grimbert, Marie Matignon
After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q binding impact on allograft survival. We compared clinical, histological, and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival...
December 19, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27990486/successful-simultaneous-liver-kidney-transplantation-in-the-presence-of-multiple-high-titered-class-i-and-ii-antidonor-hla-antibodies
#19
Flavio Paterno, Alin Girnita, Paul Brailey, David Witte, Jiang Wang, Madison C Cuffy, Tayyab Diwan, Simon Tremblay, Jane Y Revollo, Rita R Alloway, Michael R Schoech, Nadim Anwar, Shimul A Shah, Steve E Woodle
The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27990480/efficacy-of-acute-cellular-rejection-treatment-according-to-banff-score-in-kidney-transplant-recipients-a-systematic-review
#20
REVIEW
Caroline Lamarche, Jean-Maxime Côté, Lynne Sénécal, Héloïse Cardinal
BACKGROUND: The poor prognosis classically associated with Banff grade 2 acute cell-mediated rejection (CMR) may be due to unrecognized antibody-mediated damage. We thus performed a systematic review of the literature to determine the rate of response to treatment in kidney transplant recipients with pure CMR, stratified by Banff class. METHODS: In addition to a manual search, databases interrogated included Excerpta Medica Database (EMBASE), Medical Literature Analysis and Retrieval System Online (MEDLINE), Evidence-Based Medicine (EBM) databases, Central, PubMed and CINAHL...
December 2016: Transplantation Direct
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