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Chronic antibody rejection

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https://www.readbyqxmd.com/read/29767445/comparison-of-de-novo-igm-and-igg-anti-hla-dsa-between-belatacept-and-calcineurin-treated-patients-an-analysis-of-the-benefit-and-benefit-ext-trial-cohorts
#1
Matthew J Everly, Mustimbo Roberts, Robert Townsend, Robert A Bray, Howard M Gebel
Preventing conversion of donor-specific anti-HLA antibodies (DSA) from an IgM-to-IgG could a way to prevent chronic rejection. We evaluated whether belatacept-treated patients [belatacept less-intensive (LI) more-intensive (MI) regimens] have a lower rate of conversion than cyclosporine A (CsA) treated patients. We included 330 HLA mismatched patients from two phase-3 trials with either (a) complete donor/recipient HLA-A,-B,-DR, and -DQ loci typing or (b) incomplete HLA typing with IgG DSA detected pre- or post-transplant...
May 16, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29751884/acute-chronic-and-humoral-rejection-pathologic-features-under-current-immunosuppressive-regimes
#2
REVIEW
Jamie Koo, Hanlin L Wang
Under current immunosuppressive regimes, T-cell-mediated acute and chronic rejection remain common and important posttransplant complications. The definition of humoral (antibody-mediated) rejection has been greatly expanded in recent years. The histopathologic assessment of allograft biopsies continues to serve an important role in the diagnosis of rejection and to facilitate patient management. The diagnosis of both acute and chronic antibody-mediated rejection requires integration of the results of donor-specific antibody testing and C4d immunostaining, as well as exclusion of other potential etiologies of allograft dysfunction...
June 2018: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/29747114/effect-of-double-filtration-plasmapheresis-for-antibody-mediated-rejection-on-hemostasis-parameters-and-thrombin-generation
#3
R Marlu, P Malvezzi, L Seyve, T Jouve, J Maurizi, F Defendi, P L Carron, M Christophe, A Le Gouellec, B Polack, L Rostaing
INTRODUCTION: Donor-specific alloantibodies (DSAs) cause kidney-allograft loss in chronic antibody-mediated rejection (CAMR). Treatment relies on blocking antibody-producing cells and removing DSAs by apheresis: e.g., double-filtration plasmapheresis (DFPP). MATERIALS AND METHODS: To determine the impact of DFPP (6 or 8 sessions/patient) on clotting factors and natural anticoagulants, and on thrombin generation, we performed a prospective and observational study in five CAMR kidney-transplant patients who received DFPP plus rituximab therapy...
April 20, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29746495/tacrolimus-intra-patient-variability-is-not-associated-with-chronic-active-antibody-mediated-rejection
#4
Kasia A Sablik, Marian C Clahsen-van Groningen, Dennis A Hesselink, Teun van Gelder, Michiel G H Betjes
BACKGROUND: Chronic active antibody mediated rejection (c-aABMR) is a major cause of long-term kidney allograft loss. It is hypothesized that frequent sub-therapeutic exposure to immunosuppressive drugs, in particular tacrolimus (Tac), is a risk factor for the development of c-aABMR. The intra-patient variability (IPV) in Tac exposure may serve as a substitute biomarker for underexposure and/or non-adherence. In this study, the association between Tac IPV and the development of c-aABMR was investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29740433/syk-inhibition-induces-apoptosis-in-germinal-center-like-b-cells-by-modulating-the-antiapoptotic-protein-myeloid-cell-leukemia-1-affecting-b-cell-activation-and-antibody-production
#5
Nathalie Roders, Florence Herr, Gorbatchev Ambroise, Olivier Thaunat, Alain Portier, Aimé Vazquez, Antoine Durrbach
B cells play a major role in the antibody-mediated rejection (AMR) of solid organ transplants, a major public health concern. The germinal center (GC) is involved in the generation of donor-specific antibody-producing plasma cells and memory B cells, which are often poorly controlled by current treatments. Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell lymphoma-2 family, is essential for maintenance of the GC reaction and B-cell differentiation. During chronic AMR (cAMR), tertiary lymphoid structures resembling GCs appear in the rejected organ, suggesting local lymphoid neogenesis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29731924/the-spectrum-of-histopathological-changes-in-the-renal-allograft-a-12-months-protocol-biopsy-study
#6
Galina Severova-Andreevska, Ladislava Grcevska, Gordana Petrushevska, Koco Cakalaroski, Aleksandar Sikole, Olivera Stojceva-Taneva, Ilina Danilovska, Ninoslav Ivanovski
INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR)...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29731774/b7-h1-expression-is-required-for-human-endometrial-regenerative-cells-in-the-prevention-of-transplant-vasculopathy-in-mice
#7
Kui Ye, Xu Lan, Grace Wang, Baoren Zhang, Xiaoxi Xu, Xiang Li, Yiming Zhao, Hao Wang
Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN- γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro ...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29731056/clinical-significance-of-macrophage-polarization-in-antibody-mediated-rejection-of-renal-allograft
#8
J Kim, S-E Choi, B J Lim, Y S Kim, K H Huh, J Lee, S I Kim, M S Kim, H J Jeong
BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29719115/preemptive-treatment-of-early-donor-specific-antibodies-with-iga-and-igm-enriched-intravenous-human-immunoglobulins-in-lung-transplantation
#9
Fabio Ius, Murielle Verboom, Wiebke Sommer, Reza Poyanmehr, Ann-Kathrin Knoefel, Jawad Salman, Christian Kuehn, Murat Avsar, Thierry Siemeni, Caroline Erdfelder, Michael Hallensleben, Dietmar Boethig, Nicolaus Schwerk, Carsten Mueller, Tobias Welte, Christine Falk, Axel Haverich, Igor Tudorache, Gregor Warnecke
This retrospective study presents our 4-year experience of preemptive treatment of early anti-HLA donor specific antibodies with IgA- and IgM-enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between 03/2013 and 11/2017 were reviewed. The treatment protocol included one single 2g/kg immunoglobulin infusion followed by successive 0.5g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti-CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption...
May 2, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29707626/single-graft-utilization-from-donors-with-severe-acute-kidney-injury-after-circulatory-death
#10
Yusuke Tomita, Kazuhiro Iwadoh, Yuichi Ogawa, Katsuyuki Miki, Kotaro Kai, Akihito Sannomiya, Toru Murakami, Ichiro Koyama, Kumiko Kitajima, Ichiro Nakajima, Shohei Fuchinoue
Chronic shortages of organs for transplantation have led to the use of marginal kidneys from donors after circulatory death with acute kidney injury (AKI), but the utilization of kidneys with severe AKI is not well established. We retrospectively analyzed eight kidney transplantation (KTx) cases from donation after circulatory death (DCD) with terminal creatinine (t-Cr) concentrations higher than 10.0 mg/dL and/or oliguria for more than 5 days (AKI network criteria: stage III). Although all patients showed delayed graft function, no cases of primary nonfunction (PNF) were found...
April 2018: Transplantation Direct
https://www.readbyqxmd.com/read/29707618/transplantation-of-a-liver-allograft-from-a-hepatitis-c-virus-seropositive-donor-with-previous-sustained-virologic-response-to-an-uninfected-recipient-suffering-steroid-refractory-acute-graft-rejection-with-no-evidence-of-hcv-transmission
#11
Robert A Mitchell, Trana Hussaini, Alan H Yau, Mel Krajden, Alissa J Wright, Charles H Scudamore, Vladimir Marquez Azalgara, Siegfried R Erb, Eric M Yoshida
Background: The goal of treating chronic hepatitis C virus (HCV) infection is sustained virologic response (SVR). There is concern that despite achieving SVR, replication-competent HCV may be sequestered at low levels within the liver and could theoretically reactivate with immunosuppression. We report transplantation of a HCV-seropositive liver donor, who achieved SVR, into a seronegative patient without HCV reactivation despite profound immunosuppression. Method: Retrospective chart review...
March 2018: Transplantation Direct
https://www.readbyqxmd.com/read/29704327/morphological-characterization-of-chronic-antibody-mediated-rejection-in-abo-identical-or-compatible-pediatric-liver-graft-recipients
#12
Myriam Dao, Dalila Habès, Jean-Luc Taupin, Charlotte Mussini, Marie-José Redon, Caroline Suberbielle, Emmanuel Jacquemin, Emmanuel Gonzales, Catherine Guettier
ASBTRACT This study aims to define the morphological profile associated with the presence of donor-specific antibodies (DSA) and/or C4d immunostaining in ABO-identical or compatible pediatric liver grafts. Ten-year protocol liver graft biopsies performed at 131.3 ± 15.3 months post-transplantation in 53 pediatric liver graft recipients were reviewed. Immunostaining for C4d was systematically performed and semi-quantitatively analyzed. DSA were concurrently quantified and results were available for 44 patients...
April 27, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29699851/blockade-of-adhesion-molecule-lymphocyte-function-associated-antigen-1-improves-long-term-heart-allograft-survival-in-mixed-chimeras
#13
Nina Pilat, Philipp Sabler, Christoph Klaus, Benedikt Mahr, Lukas Unger, Karin Hock, Mario Wiletel, Christoph Schwarz, Ivan Kristo, Heinz Regele, Thomas Wekerle
BACKGROUND: The mixed chimerism approach for intentional induction of donor-specific tolerance was shown to be successful in various models from mice to humans. For transplant patients, the approach would obviate the need for long-term immunosuppression and associated side effects; moreover, it would preclude the risk of late graft loss due to chronic rejection. Widespread clinical application is hindered by toxicities related to recipient pre-conditioning. Herein we aimed to investigate a clinically relevant protocol for tolerance induction to cardiac allografts, sparing CD40 blockade or T-cell depletion...
March 30, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29693023/kidney-transplantation-the-challenge-of-human-leukocyte-antigen-and-its-therapeutic-strategies
#14
REVIEW
Tilahun Alelign, Momina M Ahmed, Kidist Bobosha, Yewondwossen Tadesse, Rawleigh Howe, Beyene Petros
Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29687946/does-tubulitis-without-interstitial-inflammation-represent-borderline-acute-t-cell-mediated-rejection
#15
Brian J Nankivell, Chow H P'ng, Jeremy R Chapman
Tubulitis without interstitial inflammation (Banff i0), termed "isolated tubulitis" (ISO-T), has been controversially included within the Banff "borderline" category of acute T cell mediated rejection (TCMR). This single-centre, retrospective, observational study of 2055 consecutive biopsies from 775 recipients, determined the clinical significance of ISO-T. ISO-T prevalence was 19.1%, comprising mild tubulitis (i0t1) in 97.2%. Independent clinical predictors of tubulitis were HLA mismatch, prior TCMR and antibody-mediated rejection, pulse corticosteroids, and BKVAN (P=0...
April 24, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29682370/fatal-pneumococcus-sepsis-after-treatment-of-late-antibody-mediated-kidney-graft-rejection
#16
Gunilla Einecke, Jan Hinrich Bräsen, Nils Hanke, Hermann Haller, Anke Schwarz
Antibody-mediated rejection (ABMR) is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR...
2018: Case Reports in Nephrology
https://www.readbyqxmd.com/read/29677072/state-of-the-art-role-of-the-dendritic-cell-in-induction-of-allograft-tolerance
#17
Sarah J Rosen, Paul E Harris, Mark A Hardy
Despite decades of research, the induction and maintenance of long-term allograft tolerance without immunosuppression remains an elusive goal in the field of solid organ and cell transplantation. Immunosuppressive medications frequently prevent or minimize acute cellular rejection but have failed to halt anti-donor antibody production and chronic organ rejection. Past efforts aimed at promoting lasting allograft tolerance have focused primarily on peripheral T cell depletion, augmentation of regulatory T cells, or induction via simultaneous hematopoietic stem cell transplantation and facilitation of donor chimerism...
April 19, 2018: Transplantation
https://www.readbyqxmd.com/read/29670408/acute-hepatitis-e-in-a-renal-transplantation-recipient-a-case-report
#18
Mitsutoshi Shindo, Hiroaki Takemae, Takafumi Kubo, Masatsugu Soeno, Tetsuo Ando, Yoshiyuki Morishita
Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient...
2018: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/29660004/renal-transplant-outcomes-and-de-novo-donor-specific-anti-human-leukocyte-antigen-antibodies-a-systematic-review
#19
Ankit Sharma, Joshua R Lewis, Wai H Lim, Suetonia Palmer, Giovanni Strippoli, Jeremy R Chapman, Stephen I Alexander, Jonathan C Craig, Germaine Wong
Background: Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain. Methods: We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29620612/tofacitinib-halts-progression-of-graft-dysfunction-in-a-rat-model-of-mixed-cellular-and-humoral-rejection
#20
Jordi Rovira, María J Ramírez-Bajo, Elisenda Banon-Maneus, Marta Lazo-Rodríguez, Daniel Moya-Rull, Natalia Hierro-Garcia, Valeria Tubita, Gastón J Piñeiro, Ignacio Revuelta, Pedro Ventura-Aguiar, David Cucchiari, Federico Oppenheimer, Mercè Brunet, Josep M Campistol, Fritz Diekmann
BACKGROUND: The progression from acute to chronic antibody-mediated rejection in kidney transplant recipients is usually not prevented by current therapeutic options. Here, we investigated whether the use of tofacinitib, a Janus kinase 3 inhibitor, was capable of preventing the progression of allograft dysfunction in a Fisher-to-Lewis rat model of kidney transplantation. METHODS: Rats were treated from the third week after transplantation in order to allow the development of rejection...
April 3, 2018: Transplantation
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