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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/27918373/fingering-a-natural-culprit-during-antibody-mediated-rejection
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27888573/b-cell-activating-factor-baff-a-predictor-of-antibody-mediated-rejection-in-kidney-transplantation-recipients
#11
Wannarat Pongpirul, Wiwat Chancharoenthana, Krit Pongpirul, Asada Leelahavanichakul, Wipawee Kittikowit, Kamonwan Jutivorakool, Bunthoon Nonthasoot, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa, Natavudh Townamchai
BACKGROUND: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection...
November 26, 2016: Nephrology
https://www.readbyqxmd.com/read/27888551/selective-targeting-of-high-affinity-lfa-1-does-not-augment-costimulation-blockade-in-a-nonhuman-primate-renal-transplantation-model
#12
K P Samy, D A Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer, S C Kachlany, K A Reimann, T How, F V Leopardi, K S Franke, K D Williams, B H Collins, A D Kirk
Costimulation blockade (CoB) via belatacept is a lower morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept, and increased adhesion molecule expression. One such molecule is Leukocyte Function Associated Antigen (LFA)-1. LFA-1 exists in two forms, a commonly expressed, low-affinity form, and a transient, high-affinity form, expressed only during activation...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27878627/right-ventricular-dysfunction-as-an-echocardiographic-measure-of-acute-rejection-following-heart-transplantation-in-children
#13
Sanjeev Aggarwal, Jennifer Blake, Swati Sehgal
Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic heart transplantation (OHT) are needed. The aim of this study was to investigate the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional and resistance indices in the detection of AAR. This retrospective chart review included children with biopsy-proven AAR (grade ≥ 2R cellular or CD4 + antibody-mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow tract velocity time integral ratio (TRG/VTI), were derived at baseline, during AAR and at two follow-ups...
November 23, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27873464/hyalinosis-lesions-in-renal-transplant-biopsies-time-dependent-complexity-of-interpretation
#14
Gunilla Einecke, Jeff Reeve, Philip F Halloran
Because calcineurin inhibitor immunosuppressive drugs (CNIs) induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years post-transplant. Prevalence of ah lesions increased with time post-transplant (TxBx). Ah-scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging...
November 22, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862968/the-xiii-th-banff-conference-on-allograft-pathology-the-banff-2015-heart-meeting-report-improving-antibody-mediated-rejection-diagnostics-strengths-unmet-needs-and-future-directions
#15
P Bruneval, A Angelini, D Miller, L Potena, A Loupy, A Zeevi, E F Reed, D Dragun, N Reinsmoen, R N Smith, L West, S Tebutt, T Thum, M Haas, M Mengel, P Revelo, M Fedrigo, J P Duong Van Huyen, G J Berry
The 13(th) Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5-10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semi-quantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system...
November 12, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862883/the-banff-2015-kidney-meeting-report-current-challenges-in-rejection-classification-and-prospects-for-adopting-molecular-pathology
#16
A Loupy, M Haas, K Solez, L Racusen, D Glotz, D Seron, B J Nankivell, R B Colvin, M Afrouzian, E Akalin, N Alachkar, S Bagnasco, J U Becker, L Cornell, C Drachenberg, D Dragun, H De Kort, I W Gibson, E S Kraus, C Lefaucheur, C Legendre, H Liapis, T Muthukumar, V Nickeleit, B Orandi, W Park, M Rabant, P Randhawa, E F Reed, C Roufosse, S V Seshan, B Sis, H K Singh, C Schinstock, A Tambur, A Zeevi, M Mengel
The XIII. Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection, requires further consensus agreement and validation in biopsies...
November 10, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862703/alemtuzumab-campath-1h-therapy-for-refractory-rejections-in-pediatric-heart-transplant-recipients
#17
Bibhuti Das, Vivian Dimas, Kristine Guleserian, Chantale Lacelle, Kristin Anton, Lindy Moore, Robert Morrow
Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath-1H) in six consecutive patients with refractory rejection. These rejection episodes persisted despite conventional treatment, which included intravenous methylprednisolone, rituximab, immunoglobulin G, and antithymocyte globulin. In our series, after ALE therapy, LV SF increased from 22%±5% to 33%±5% (P=.01). However, in our series, ALE therapy neither led to persistent LV function recovery nor could it prevent subsequent antibody-mediated rejection...
November 11, 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/27858192/rethinking-peritubular-capillary-basement-membrane-multilayering-in-renal-transplant-pathology-a-case-report
#18
Diana Maria Lopategui, Evelyne Lerut, Maarten Naesens, Rita Van Damme-Lombaerts, Elena Levtchenko, Noël Knops
BACKGROUND: Severe multilayering (ML) of the peritubular capillary basement membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML. METHODS: The patient received a kidney from his mother, whose donor screening was unremarkable...
November 17, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27855166/a-comparison-of-two-types-of-rabbit-antithymocyte-globulin-induction-therapy-in-immunological-high-risk-kidney-recipients-a-prospective-randomized-control-study
#19
F Burkhalter, S Schaub, Ch Bucher, L Gürke, A Bachmann, H Hopfer, M Dickenmann, J Steiger, I Binet
BACKGROUND: Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy...
2016: PloS One
https://www.readbyqxmd.com/read/27849166/first-in-human-study-in-healthy-subjects-with-fr104-a-pegylated-monoclonal-antibody-fragment-antagonist-of-cd28
#20
Nicolas Poirier, Gilles Blancho, Maryvonne Hiance, Caroline Mary, Tim Van Assche, Jos Lempoels, Steven Ramael, Weirong Wang, Virginie Thepenier, Cecile Braudeau, Nina Salabert, Regis Josien, Ian Anderson, Ian Gourley, Jean-Paul Soulillou, Didier Coquoz, Bernard Vanhove
FR104 is a monovalent pegylated Fab' Ab, antagonist of CD28, under development for treatment of transplant rejection and autoimmune diseases. In contrast to CD80/86 antagonists (CTLA4-Ig), FR104 selectively blunts CD28 costimulation while sparing CTLA-4 and PD-L1 coinhibitory signals. In the present work, FR104 has been evaluated in a first-in-human study to evaluate the safety, pharmacokinetics, pharmacodynamics, and potency of i.v. administrations in healthy subjects. Sixty-four subjects were randomly assigned to four single ascending dose groups, two double dose groups and four single ascending dose groups challenged with keyhole limpet hemocyanin...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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