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https://www.readbyqxmd.com/read/29319615/clinical-and-pathological-features-of-plasma-cell-rich-acute-rejection-after-kidney-transplantation
#1
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/29300203/evolving-criteria-for-the-diagnosis-of-antibody-mediated-rejection-in-renal-allografts
#2
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/29245962/associations-between-hvem-light-btla-cd160-polymorphisms-and-the-occurrence-of-antibody-mediate-rejection-in-renal-transplant-recipients
#3
Zijie Wang, Ke Wang, Haiwei Yang, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Miao Guo, Chuanjian Suo, Ji-Fu Wei, Ruoyun Tan, Min Gu
Antibody-mediated rejection (ABMR) is a serious complications that can occur following renal transplantation. The production of donor-specific antibodies by the humoral immune response can trigger costimulatory signals, which are crucial in activating immune cells, and therefore, playing a potential role in ABMR. To investigate the role of HVEM/LIGHT/BTLA/CD160 polymorphisms in ABMR, we retrospectively analyzed 200 renal transplant recipients. We adopted next-generation sequencing (NGS) to identify HVEM/LIGHT/BTLA/CD160 single-nucleotide polymorphisms (SNPs) in the genotypes of these patients...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29243394/the-banff-2017-kidney-meeting-report-revised-diagnostic-criteria-for-chronic-active-t-cell-mediated-rejection-antibody-mediated-rejection-and-prospects-for-integrative-endpoints-for-next-generation-clinical-trials
#4
M Haas, A Loupy, C Lefaucheur, C Roufosse, D Glotz, D Seron, B J Nankivell, P F Halloran, R B Colvin, N Alachkar, S Bagnasco, Y Bouatou, J U Becker, L Cornell, J P Duong van Huyen, I Gibson, R Mannon, M Naesens, V Nickeleit, P Nickerson, D L Segev, H K Singh, M Stegall, P Randhawa, L Racusen, K Solez, M Mengel
The kidney sessions of the 2017 Banff Conference focused on two areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by two groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with under-immunosuppression...
December 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29242250/a-randomized-trial-of-bortezomib-in-late-antibody-mediated-kidney-transplant-rejection
#5
Farsad Eskandary, Heinz Regele, Lukas Baumann, Gregor Bond, Nicolas Kozakowski, Markus Wahrmann, Luis G Hidalgo, Helmuth Haslacher, Christopher C Kaltenecker, Marie-Bernadette Aretin, Rainer Oberbauer, Martin Posch, Anton Staudenherz, Ammon Handisurya, Jeff Reeve, Philip F Halloran, Georg A Böhmig
Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR...
December 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29212248/impact-of-complement-component-3-4-5-single-nucleotide-polymorphisms-on-renal-transplant-recipients-with-antibody-mediated-rejection
#6
Zijie Wang, Haiwei Yang, Miao Guo, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu
Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction in kidney transplantation. The complement system is considered to be associated with the generation of alloreative antibodies and donor-specific antibodies. However, the association of complement single nucleotide polymorphisms (SNPs) with ABMR still remained unclear. Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected, and analyzed by next-generation sequencing with an established gene panel...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29178397/review-the-transcripts-associated-with-organ-allograft-rejection
#7
Philip F Halloran, Jeffery M Venner, Katelynn Madill-Thomsen, Gunilla Einecke, Michael Parkes, Luis G Hidalgo, Konrad S Famulski
The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants...
November 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29159992/clinical-and-histopathologic-features-of-antibody-mediated-rejection-among-pediatric-renal-transplant-recipients-with-preformed-vs-de-novo-donor-specific-antibodies
#8
Justin A Steggerda, Irene K Kim, Mark Haas, Xiaohai Zhang, Alexis Kang, Helen Pizzo, Elaine Kamil, Stanley Jordan, Dechu Puliyanda
Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy-proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow-up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA...
December 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#9
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29109529/glomerulocapillary-mirna-response-to-hla-class-i-antibody-in-vitro-and-in-vivo
#10
Falko M Heinemann, Peter T Jindra, Clemens L Bockmeyer, Philip Zeuschner, Juliane Wittig, Heike Höflich, Marc Eßer, Mahmoud Abbas, Georg Dieplinger, Katharina Stolle, Udo Vester, Peter F Hoyer, Stephan Immenschuh, Andreas Heinold, Peter A Horn, Wentian Li, Ute Eisenberger, Jan U Becker
Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#11
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28949089/treatment-of-chronic-antibody-mediated-rejection-with-intravenous-immunoglobulins-and-rituximab-a-multicenter-prospective-randomized-double-blind-clinical-trial
#12
Francesc Moreso, Marta Crespo, Juan C Ruiz, Armando Torres, Alex Gutierrez-Dalmau, Antonio Osuna, Manel Perelló, Julio Pascual, Irina B Torres, Dolores Redondo-Pachón, Emilio Rodrigo, Marcos Lopez-Hoyos, Daniel Seron
There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m(2) and/or severe interstitial fibrosis/tubular atrophy were excluded...
September 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#13
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28929636/risk-factors-for-the-development-of-antibody-mediated-rejection-in-highly-sensitized-pediatric-kidney-transplant-recipients
#14
Irene K Kim, Jua Choi, Ashley Vo, Alexis Kang, Justin Steggerda, Sabrina Louie, Mark Haas, James Mirocha, J Louis Cohen, Helen Pizzo, Elaine S Kamil, Stanley C Jordan, Dechu Puliyanda
ABMR remains a significant concern for early graft loss, especially for those who are HS against HLA antigens. We sought to determine the risk factors leading to ABMR in HS pediatric kidney transplant recipients. From January 2009 to December 2015, 16 HS pediatric kidney transplant patients at our center (age range 2-21) were retrospectively reviewed for outcomes and risk factors for ABMR. All HS patients received desensitization with high-dose IVIG/rituximab prior to transplant. Two groups were examined: ABMR+ (n = 7) and ABMR- (n = 9)...
December 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#15
REVIEW
Neetika Garg, Milagros D Samaniego, Dana Clark, Arjang Djamali
The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause)...
October 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28858176/midterm-outcomes-of-12-renal-transplant-recipients-treated-with-eculizumab-to-prevent-atypical-hemolytic-syndrome-recurrence
#16
Charlène Levi, Véronique Frémeaux-Bacchi, Julien Zuber, Marion Rabant, Magali Devriese, Renaud Snanoudj, Anne Scemla, Lucile Amrouche, Arnaud Mejean, Christophe Legendre, Rebecca Sberro-Soussan
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab. METHODS: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25)...
August 25, 2017: Transplantation
https://www.readbyqxmd.com/read/28833936/persistent-c4d-and-antibody-mediated-rejection-in-pediatric-renal-transplant-patients
#17
Andrew M South, Lynn Maestretti, Neeraja Kambham, Paul C Grimm, Abanti Chaudhuri
Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow-up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12 months was a composite of ≥50% reduction in eGFR, transplant glomerulopathy, or graft failure...
November 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#18
J A Steggerda, A Kang, S-H Pan, V Sundaram, N N Nissen, A S Klein, T Todo, A Annamalai, A Vo, S C Jordan, I K Kim
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28664838/treatment-of-antibody-mediated-rejection-of-kidney-grafts-with-bortezomib-and-or-rituximab-compared-to-standard-regimen-experience-of-slovene-national-center
#19
Teja Oblak, Jelka Lindič, Jakob Gubenšek, Radoslav Kveder, Andreja Aleš Rigler, Andrej Škoberne, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin, Rafael Ponikvar, Gregor Mlinšek, Dušan Ferluga, Nika Kojc, Uroš Godnov, Damjan Kovač
BACKGROUND: The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab. METHODS: The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 - 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab...
2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28662985/building-a-tissue-based-molecular-diagnostic-system-in-heart-transplant-rejection-the-heart-molecular-microscope-diagnostic-mmdx-system
#20
Philip F Halloran, Luciano Potena, Jean-Paul Duong Van Huyen, Patrick Bruneval, Ornella Leone, Daniel H Kim, Xavier Jouven, Jeff Reeve, Alexandre Loupy
BACKGROUND: The emergence of molecular systems offers opportunities for improving the assessment of rejection in heart transplant biopsy specimens. The present study developed a microarray-based system for assessing heart transplant endomyocardial biopsy (EMB) specimens. METHODS: We analyzed 331 protocol or for-cause EMB specimens from 221 subjects in 3 centers (Edmonton, Bologna, and Paris). Unsupervised principal component analysis (PCA) and archetype analysis used rejection-associated transcripts (RATs) shown in kidney transplants to be associated with antibody-mediated rejection (ABMR) or T cell-mediated rejection (TCMR), or both...
November 2017: Journal of Heart and Lung Transplantation
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