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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/28421272/-the-pathology-of-adverse-events-with-immune-checkpoint-inhibitors
#1
V H Koelzer, K Glatz, L Bubendorf, A Weber, A Gaspert, G Cathomas, A Lugli, A Zippelius, W Kempf, K D Mertz
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs...
April 18, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28419995/hemolytic-uremic-syndrome-and-kidney-transplantation-a-case-series-and-review-of-the-literature
#2
Sabrina Milan Manani, Grazia Maria Virzì, Anna Giuliani, Anna Clementi, Alessandra Brocca, Daniela Dissegna, Francesca Martino, Emanuele Stefano Giovanni d'Amore, Claudio Ronco
BACKGROUND: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation...
April 19, 2017: Nephron
https://www.readbyqxmd.com/read/28407877/simultaneous-liver-kidney-transplantation-shifting-renal-allograft-gene-expression-from-inflammation-toward-preservation
#3
Mark Haas
Exposure of renal allografts to donor-specific antibodies activates many proinflammatory genes, resulting in antibody-mediated rejection. Simultaneous liver transplantation reduces the development of antibody-mediated rejection in renal grafts exposed to donor-specific antibodies. A study by Taner et al. in this issue of Kidney International shows this effect of the liver to involve more than simply absorbing donor-specific antibodies, with a shift in the pattern of gene expression in the kidney away from proinflammatory toward preservation of tissue function...
May 2017: Kidney International
https://www.readbyqxmd.com/read/28405599/absence-of-intragraft-b-cells-in-rejection-biopsies-after-rituximab-induction-therapy-consequences-for-clinical-outcome
#4
Martijn W F van den Hoogen, Eric J Steenbergen, Marije C Baas, Sandrine Florquin, Luuk B Hilbrands
BACKGROUND: The pathophysiological role of intragraft B cells during renal allograft rejection is unclear. METHODS: We studied B-cell infiltration during acute rejection in 53 patients who participated in a clinical trial in which adult renal transplant patients were randomized between a single intraoperative dose of rituximab (375 mg/m(2)) or placebo as induction therapy. Two independent pathologists scored all biopsies in a blinded fashion according to the Banff classification and scored for the presence of B cells and plasma cells using CD79a and CD138 as markers...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28403566/outcomes-and-risk-stratification-for-late-antibody-mediated-rejection-in-recipients-of-abo-incompatible-kidney-transplants
#5
Bonnie E Lonze, Sunjae Bae, Edward S Kraus, Mary J Holechek, Karen E King, Nada Alachkar, Fizza F Naqvi, Nabil N Dagher, Adnan Sharif, Niraj M Desai, Dorry L Segev, Robert A Montgomery
The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA-incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR...
April 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28396194/the-use-of-kinase-inhibitors-in-solid-organ-transplantation
#6
REVIEW
S Dholakia, J E Fildes, P J Friend
INTRODUCTION: Despite the efficacy of current immunosuppression regimes used in solid organ transplantation, graft dysfunction, graft lost and antibody-mediated rejection continue to be problematic. As a result, clear attraction in exploiting key potential targets controlled by kinase phosphorylation has led to a number of studies exploring the use of these drugs in transplantation. Aim In this review, we consider the role of tyrosine kinase as a target in transplantation and summarize the relevant studies on kinase inhibitors that have been reported to date...
March 25, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28393447/anti-cd40-antibody-mediated-costimulation-blockade-promotes-long-term-survival-of-deep-lamellar-porcine-corneal-grafts-in-non-human-primates
#7
Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Mee Kum Kim, Won Ryang Wee
BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28390683/prognostic-utility-of-right-ventricular-free-wall-strain-in-low-risk-patients-after-orthotopic-heart-transplantation
#8
Amr F Barakat, Brett W Sperry, Randall C Starling, Amgad Mentias, Zoran B Popovic, Brian P Griffin, Milind Y Desai
Global longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive measure of regional left and right ventricular (LV and RV) dysfunction, before onset of overt systolic dysfunction. We sought to evaluate the prognostic utility of measuring LV-GLS and RV free wall strain (FWS) in low risk patients at 1 year after orthotopic heart transplantation (OHT). We retrospectively studied 96 OHT recipients (age 52 ± 14 years, 64% men) free of antibody-mediated rejection or moderate to severe coronary allograft vasculopathy (CAV, grade 2 to 3) at 1 year after transplant...
March 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28378521/defining-the-immunogenicity-and-antigenicity-of-hla-epitopes-is-crucial-for-optimal-epitope-matching-in-clinical-renal-transplantation
#9
REVIEW
C S M Kramer, D L Roelen, S Heidt, F H J Claas
Transplantation of an human leukocyte antigen (HLA) mismatched graft can lead to the development of donor-specific antibodies (DSA), which can result in antibody mediated rejection and graft loss as well as complicate repeat transplantation. These DSA are induced by foreign epitopes present on the mismatched HLA antigens of the donor. However, not all epitopes appear to be equally effective in their ability to induce DSA. Understanding the characteristics of HLA epitopes is crucial for optimal epitope matching in clinical transplantation...
April 5, 2017: HLA
https://www.readbyqxmd.com/read/28373996/not-all-antibodies-are-created-equal-factors-that-influence-antibody-mediated-rejection
#10
REVIEW
Carrie L Butler, Nicole M Valenzuela, Kimberly A Thomas, Elaine F Reed
Consistent with Dr. Paul Terasaki's "humoral theory of rejection" numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR) and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28372986/assessing-the-potential-of-angiotensin-ii-type-1-receptor-and-donor-specific-anti-endothelial-cell-antibodies-to-predict-long-term-kidney-graft-outcome
#11
David F Pinelli, John J Friedewald, Kelley M K Haarberg, Shree L Radhakrishnan, Jennifer R Zitzner, Wendy Wegner, Anat R Tambur
Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to Angiotensin II - Type 1 Receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years...
March 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/28367453/de-novo-donor-specific-hla-antibodies-developing-early-or-late-after-transplant-are-associated-with-the-same-risk-of-graft-damage-and-loss-in-nonsensitized-kidney-recipients
#12
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago, Antonella Gurrado, Ilaria Guido, Francesca Compagno, Giacomo Garibotto, Catherine Klersy, Enrico Verrina, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, Fabrizio Ginevri
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28363404/acute-antibody-mediated-rejection-following-sleeve-gastrectomy-in-a-kidney-transplant-recipient-treated-with-a-belatacept-mycophenolate-mofetil-based-therapy
#13
Jamale Rizkallah, Nassim Kamar, Arnaud Del Bello
No abstract text is available yet for this article.
February 24, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28361123/tocilizumab-anti-il-6r-suppressed-tnf%C3%AE-production-by-human-monocytes-in-an-in-vitro-model-of-anti-hla-antibody-induced-antibody-dependent-cellular-cytotoxicity
#14
Bong-Ha Shin, Shili Ge, James Mirocha, Stanley C Jordan, Mieko Toyoda
BACKGROUND: We previously demonstrated that natural killer (NK) cells activated via FcγRIIIa (CD16) interactions with anti-HLA antibodies binding to peripheral blood mononuclear cells (PBMCs) in the in vitro antibody-dependent cellular cytotoxicity (ADCC) assay produced IFNγ. Here we investigate if other CD16 bearing cells are responsive to alloantigen via alloantibody in the in vitro ADCC and if the ADCC-induced cytokine reactions and cytotoxicity can be modified by the anti-interleukin 6 receptor (IL-6R) monoclonal antibody, Tocilizumab (TCZ)...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28361120/acute-rejection-phenotypes-in-the-current-era-of-immunosuppression-a-single-center-analysis
#15
Caroline Wehmeier, Patrizia Amico, Patricia Hirt-Minkowski, Argyrios Georgalis, Gideon Höenger, Thomas Menter, Michael Mihatsch, Felix Burkhalter, Juerg Steiger, Michael Dickenmann, Helmut Hopfer, Stefan Schaub
BACKGROUND: Besides 'definitive rejection', the Banff classification includes categories for 'suspicious for rejection' phenotypes. The aim of this study was to determine the frequency and phenotypes of rejection episodes in 316 consecutive renal transplants from 2009 to 2014 grouped into patients without/with pretransplant HLA-DSA (ptDSAneg, n = 251; ptDSApos, n = 65). METHODS: All adequate indication (n = 125) and surveillance biopsies (n = 538) performed within the first year posttransplant were classified according to the current Banff criteria...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28348361/the-impact-of-donor-specific-anti-human-leukocyte-antigen-hla-antibody-rebound-on-the-risk-of-antibody-mediated-rejection-in-sensitized-kidney-transplant-recipients
#16
Kyo Won Lee, Jae Berm Park, Chan Woo Cho, Nuri Lee, Heejin Yoo, Kyunga Kim, Hyojun Park, Eun Suk Kang, Wooseong Huh, Sungjoo Kim
BACKGROUND Donor-specific anti-HLA antibody (DSA) detected on Luminex-based single antigen assay (LSA) has become the subject of desensitization based upon the results of previous studies. We retrospectively investigated the impact of preoperative DSA on the incidence of antibody mediated rejection (AMR) in patients desensitized using a protocol based on rituximab and rabbit antithymocyte globulin (rATG). MATERIAL AND METHODS Nine patients (Group 1, 9/327, 2.8%) were complement dependent cytotoxicity crossmatch (CDC-XM) positive and underwent desensitization with rituximab (375 mg/m²), intravenous immunoglobulin (IVIG; 400 mg/kg), plasmapheresis, and rATG...
March 28, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#17
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28340816/relevance-of-flow-cytometric-auto-crossmatch-to-the-post-transplant-course-of-kidney-transplant-recipients
#18
E Demir, O Yeğit, A Erol, S U Akgül, B Çalışkan, A Bayraktar, Y Çalışkan, A Türkmen, F O Savran, M S Sever
INTRODUCTION: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340811/tac-mmf-versus-csa-mmf-csa-aza-based-regimens-in-development-of-de-novo-complement-binding-anti-hla-antibodies-after-kidney-transplantation
#19
T Sahutoglu, S U Akgul, Y Caliskan, H Yazici, E Demir, E Kara, S Temurhan, F O Savran, A Turkmen
BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28339922/therapeutic-plasma-exchange-for-potential-human-leukocyte-antigen-antibody-mediated-rejection-in-liver-transplant-patients
#20
Eric Salazar, David Cohen, Tina Ipe, Christopher Leveque
No abstract text is available yet for this article.
March 1, 2017: American Journal of Clinical Pathology
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