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Antibody mediated rejection

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https://www.readbyqxmd.com/read/27932156/dosing-eculizumab-for-antibody-mediated-rejection-in-kidney-transplantation-a-case-report
#1
B Smith, V Kumar, D Mompoint-Williams, R D Reed, P A MacLennan, K Stegner, J E Locke
Severe antibody-mediated rejection (AMR) of a blood type-incompatible (ABOi) living donor kidney transplantation (LDKT) can lead to graft failure, and aggressive therapies, such as the anticomplement antibody eculizumab, are often used to rescue the affected graft. Eculizumab therapy can be crippling financially. Current literature suggests a wide variation in the amount and timing of eculizumab given as rescue therapy in the setting of AMR. Herein we describe a limited-eculizumab regimen in the setting of severe AMR that is both clinically and cost effective...
November 2016: Transplantation Proceedings
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
#2
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/27932139/de-novo-anti-hla-antibodies-after-heart-transplantation-are-associated-with-adverse-events-in-the-long-term-follow-up-of-cardiac-transplant-recipients
#3
E Solé-González, S Mirabet, V Brossa, L López-López, M Rivas-Lasarte, H Capellades-Olivella, A J Ginel-Iglesias, J Martorell-Pons, E Roig
BACKGROUND AND OBJECTIVES: Long-term morbidity and mortality after heart transplantation (HTx) remain very high. Several reports have suggested that anti-HLA antibodies (anti-HLA-AB) detected after HTx might be associated with poor survival, but the implication of isolated anti-HLA-AB is still under debate. The aim of the study was to analyze the incidence of de novo anti-HLA-AB and whether they are associated with adverse events after HTx. METHODS: This retrospective study analyzed the presence of anti-HLA-AB assessed by fluorimetry (Luminex) and quantified by a single-antigen bead assay in 119 HTx patients...
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
#4
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/27932107/antibody-mediated-acute-vascular-rejection-of-kidney-allografts-fifteen-year-follow-up
#5
B Rodríguez Cubillo, I Pérez Flores, N Calvo, A Pascual, J A Cortés, M A Moreno, J Blanco, A Sánchez Fructuoso
BACKGROUND: Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or humoral rejection (AHR) has dissimilar outcomes. The aim of this study was to examine the association between subtypes of AVR and graft loss. METHODS: We assessed patients who provided biopsy samples for acute allograft rejection from 1998 to 2014. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology as well as donor-specific anti-HLA antibodies when available...
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
#6
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/27932102/kidney-transplantation-results-in-very-highly-sensitized-patients-included-in-a-virtual-crossmatch-program-analysis-of-kidney-pairs
#7
A Mazuecos, A Alvarez, A Nieto, M A Gentil, M Cabello, A Rodriguez-Benot, C Gracia, F Gonzalez, P Castro, M Alonso
BACKGROUND: Kidney transplantation in highly-sensitized (HS) patients can improve with organ-exchange strategies based on virtual crossmatch (V-XM). Experience in very-HS patients is limited. METHODS: In June 2012, Andalusia started a V-XM protocol for very-HS patients (calculated panel reactive antibodies ≥95%). After organ allocation a cytotoxic-XM performed immediately before transplantation had to be negative for surgery to proceed. We analyzed results up until December 2015...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932099/antibody-mediated-rejection-in-kidney-transplantation-without-evidence-of-anti-hla-antibodies
#8
J Irure, M López-Hoyos, E Rodrigo, J Gómez-Román, J C Ruiz, M Arias, D San Segundo
INTRODUCTION: The definition of antibody-mediated rejection (AMR) is based on serologic (presence and/or development of donor-specific anti-HLA antibodies [DSAs]) and histologic (C4d deposition and endothelial damage) criteria. However, several cases of AMR have been described without C4d deposition, and other cases of histologic AMR without DSAs, which could be driven by other non-HLA alloantibodies such as anti-MICA or anti-angiotensin II type I receptor (AT1R). Here we studied clinical and histologic humoral rejection in kidney transplant recipients without evidence of anti-HLA antibodies...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931587/do-prior-driveline-infections-increase-the-risk-of-infection-in-heart-transplant-patients-treated-with-rabbit-antithymocyte-globulin-induction-therapy
#9
D Arman, D Kuraitis, J Moriguchi, M Hamilton, F Liou, S Siddiqui, M Luu, P Zakowski, F Arabia, J Kobashigawa
BACKGROUND: The use of mechanical circulatory support devices (MCSDs) has been increasing over the past several years. Driveline infections (DLIs) are one of the most common complications seen in these patients; reportedly, up to 50% of patients with MCSDs can develop this complication. It is believed that the removal of the driveline results in treatment of the localized infection area. MCSD patients are also known to develop circulating antibodies. These circulating antibodies have been associated with poor outcomes after heart transplantation...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931512/xenotransplanted-pig-sertoli-cells-inhibit-both-the-alternative-and-classical-pathways-of-complement-mediated-cell-lysis-while-pig-islets-are-killed
#10
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SCs) survive xenotransplantation long term (90 days) without immunosuppression, making SCs an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies and the activation of the complement cascade. Using an in vitro cytotoxicity assay, wherein cells were cultured with human serum and complement, we demonstrated that neonatal pig SCs (NPSCs) are resistant to complement-mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46), and decay-accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPIs), which served as non-immune-privileged controls...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27918373/fingering-a-natural-culprit-during-antibody-mediated-rejection
#11
Robert L Fairchild
No abstract text is available yet for this article.
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27918214/immunosuppression-and-adult-heart-transplantation-emerging-therapies-and-opportunities
#12
Nicholas Furiasse, Jon A Kobashigawa
Immunosuppression following heart transplantation has improved graft longevity through the reduction of cellular and antibody mediated rejection. The attempt to limit the unintended consequences of immunosuppressive therapies and address sensitized patients has led to a revolution in immunosuppression. Areas Covered: This review will focus on the current emerging immunosuppressive therapies in heart transplantation while reviewing the effective contemporary treatments, and explore the potential development of new immunomodulatory therapies...
December 5, 2016: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/27916323/donor-specific-anti-hla-antibodies-with-antibody-mediated-rejection-and-long-term-outcomes-following-heart-transplantation
#13
Kevin J Clerkin, Maryjane A Farr, Susan W Restaino, Emmanuel Zorn, Farhana Latif, Elena R Vasilescu, Charles C Marboe, Paolo C Colombo, Donna M Mancini
BACKGROUND: Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist. METHODS: From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis...
November 17, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#14
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
#15
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/27906829/evidence-for-cd16a-mediated-nk-cell-stimulation-in-antibody-mediated-kidney-transplant-rejection
#16
Michael D Parkes, Philip F Halloran, Luis G Hidalgo
BACKGROUND: Natural killer (NK) cells localize in the microcirculation in antibody-mediated rejection (ABMR) and have been postulated to be activated by donor-specific anti-HLA antibodies triggering their CD16a Fc receptors. However, direct evidence for NK cell CD16a triggering in ABMR is lacking. We hypothesized that CD16a-inducible NK cell-selective transcripts would be expressed in human ABMR biopsies and would offer evidence for CD16a triggering. METHODS: We stimulated human NK cells through CD16a in vitro, characterized CD16a-inducible transcripts, and studied their expression in human kidney transplant biopsies with ABMR and in an extended human cell panel to determine their selectivity...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27900974/disseminated-mycobacteria-chelonae-infection-in-a-kidney-pancreas-transplant-recipient-a-case-report-and-review-of-the-literature
#17
Shafi Malik, Ananda Ghosh, Shahid Husain
A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg)...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27898462/recent-advances-in-allograft-vasculopathy
#18
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)...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27894836/use-of-complement-binding-assays-to-assess-the-efficacy-of-antibody-mediated-rejection-therapy-and-prediction-of-graft-survival-in-kidney-transplantation
#19
Daniel S Ramon, Yihung Huang, Lili Zhao, TrisAnn Rendulic, Jeong M Park, Randall S Sung, Milagros Samaniego
BACKGROUND: The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR...
November 25, 2016: Human Immunology
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
#20
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
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