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Antibody mediated rejection

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https://www.readbyqxmd.com/read/29149956/comparison-between-total-igg-c1q-and-c3d-single-antigen-bead-assays-in-detecting-class-i-complement-binding-anti-hla-antibodies
#1
M A Moreno Gonzales, D G Mitema, B H Smith, C A Schinstock, M D Stegall, L L Wakefield, N A Henderson, S R DeGoey, J D Kreuter, M J Gandhi
BACKGROUND: Complement-binding donor-specific antibodies (DSAs) are associated with antibody-mediated rejection and allograft loss. Novel single antigen bead (SAB) assays-that is, complement component 1q (C1q) and complement component 3d (C3d) assays-have been developed to specifically detect complement-binding DSA, but it remains unclear whether these assays have an improved ability to detect complement-binding DSA as compared with using the total IgG SAB assay with a high mean fluorescence intensity (MFI) cutoff...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29146602/donor-specific-and-nonspecific-hla-antibodies-and-outcome-post-lung-transplantation
#2
Stijn E Verleden, Bart M Vanaudenaerde, Marie-Paul Emonds, Dirk E Van Raemdonck, Arne P Neyrinck, Geert M Verleden, Robin Vos
Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are associated with chronic lung allograft dysfunction (CLAD) and mortality post lung transplantation, but data concerning prevalence, time of onset, persistence and effects on long-term outcome remain scarce.We assessed the association between HLA antibodies and CLAD-free and graft survival in a cohort of 362 patients. We stratified our analysis according to DSA status, persistence of antibodies and timing of antibodies (pre-transplant, early or late post-transplant)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29145577/photodynamic-therapy-leads-to-time-dependent-regression-of-pathologic-corneal-lymph-angiogenesis-and-promotes-high-risk-corneal-allograft-survival
#3
Yanhong Hou, Viet Nhat Hung Le, Thomas Clahsen, Ann-Charlott Schneider, Felix Bock, Claus Cursiefen
Purpose: Pathologic corneal (lymph) angiogenesis is a known risk factor for immune-mediated allograft rejections after corneal transplantation. However, there is no established treatment to regress pre-existing pathological corneal blood and lymphatic vessels. This study assessed the possibility to regress both vessel types by photodynamic therapy (PDT) after intravenous (i.v.) verteporfin injection, the influence of timing of PDT after verteporfin injection, and the effect on graft survival in high-risk keratoplasty...
November 1, 2017: Investigative Ophthalmology & Visual Science
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
#4
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/29128017/acute-rejection-and-antibody-mediated-rejection-in-lung-transplantation
#5
REVIEW
Ramsey R Hachem
Despite advances in immunosuppression over the past 25 years, acute cellular rejection remains a common complication early after lung transplantation. Although acute cellular rejection has often not resulted in clinical signs or symptoms of allograft dysfunction, it has been widely recognized as a strong independent risk factor for the development of chronic rejection, emphasizing its clinical significance. In recent years, the role of humoral immunity in lung rejection has been increasingly appreciated, and antibody-mediated rejection is now recognized as a form of rejection that may result in allograft failure...
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29120508/synthesis-and-immunological-evaluation-of-a-multicomponent-cancer-vaccine-candidate-containing-a-long-muc1-glycopeptide
#6
Geert-Jan Boons, Nitin T Supekar, Vani Lakshminarayanan, Chantelle J Capicciotti, Anju Sirohiwal, Cathy S Madsen, Margreet A Wolfert, Peter A Cohen, Sandra J Gendler
A fully synthetic MUC1-based cancer vaccine has been designed and chemically synthesized that contains an endogenous helper T-epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). It also activated cytotoxic T-lymphocytes and collectively the immunological data demonstrate engagement of helper T-cells in immune activation. A synthetic methodology was developed for a penta-glycosylated MUC1 glycopeptide and anti-sera of mice immunized by the new vaccine recognized such a structure...
November 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29110793/postoperative-management-of-heart-transplantation-patients
#7
REVIEW
Eleanor Vega, Jacob Schroder, Alina Nicoara
Heart transplant recipients are at risk for a number of post-transplantation complications such as graft dysfunction, rejection, and infection. The rates of many complications are decreasing over time, and prognosis is improving. However, these patients continue to experience significant morbidity and mortality. This review focuses on the optimal management of heart transplant recipients in the postoperative period, based on current knowledge. More information is needed about the best ways to predict, prevent, and treat primary graft dysfunction, right ventricular failure, and cellular and antibody-mediated rejection...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/29109529/glomerulocapillary-mirna-response-to-hla-class-i-antibody-in-vitro-and-in-vivo
#8
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/29103970/detection-of-retinal-pigment-epithelium-specific-antibody-in-ipsc-derived-retinal-pigment-epithelium-transplantation-models
#9
Sunao Sugita, Kenichi Makabe, Shota Fujii, Yuko Iwasaki, Hiroyuki Kamao, Takashi Shiina, Kazumasa Ogasawara, Masayo Takahashi
Antibody-mediated rejection is characterized by donor-specific antibody produced by B cells. However, to our knowledge, B cell invasion and antibody in the inflamed retina after transplantation of retinal pigment epithelial (RPE) cells has not been reported. To determine if RPE transplantation could be performed using allografts, we established in vivo immune rejection models with induced pluripotent stem cell (iPSC)-RPE allografts and determined whether RPE-specific antibody could be detected in these models...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29101003/fatal-accelerated-rejection-with-a-prominent-natural-killer-cell-infiltrate-in-a-heart-transplant-recipient-with-peripartum-cardiomyopathy
#10
Ali Javaheri, Amber R Wang, Eline Luning Prak, Priti Lal, Lee R Goldberg, Malek Kamoun
Accelerated rejection is uncommon after cardiac transplantation. The mechanism is hypothesized to be mediated by cytotoxic T cells and anti-HLA antibodies resulting from a memory response to the donor allograft in sensitized patients. A role for Natural Killer (NK) cell in cellular rejection has also been suggested. We report a case of fulminant accelerated rejection in a heart transplant recipient, with a history of peripartum cardiomyopathy (PPMC). The patient had no pre-transplant donor specific antibody and flow cytometric T and B cell crossmatches were negative...
October 31, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/29093713/cardiac-non-human-leukocyte-antigen-identification-techniques-and-troubles
#11
REVIEW
Katherine V Gates, Naveen L Pereira, Leigh G Griffiths
Historically efforts have focused on the human leukocyte antigen (HLA) as the major cause for acute and chronic rejection following cardiac transplantation. However, rising evidence indicates that non-HLA antibodies can be both primary initiators and modifiers of antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). The purpose of this review is to assess currently available technologies for non-HLA identification and leveraging such responses toward antibody quantification. Several techniques have been used to identify antigenic determinants of recipient graft-specific non-HLA humoral immune responses, but each comes with its own set of benefits and caveats...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29089163/peripheral-blood-detection-of-systemic-graft-specific-xeno-antibodies-following-transplantation-of-human-neural-progenitor-cells-into-the-porcine-spinal-cord
#12
Jason J Lamanna, Juanmarco Gutierrez, Jaclyn R Espinosa, Jacob Wagner, Lindsey N Urquia, Cheryl Moreton, C Victor Hurtig, Muhibullah Tora, Allan D Kirk, Thais Federici, Nicholas M Boulis
Extensive pre-clinical and clinical studies have searched for therapeutic efficacy of cell-based therapeutics in diseases of the Central Nervous System (CNS) with no other viable options. Allogeneic cells represent the primary source of these therapies and immunosuppressive regimens have been empirically employed based on experience with solid organ transplantation, attempting to avoid immune mediated graft rejection. In this study, we aimed to 1) characterize the host immune response to stem cells transplanted into the CNS and 2) develop a non-invasive method for detecting immune response to transplanted cell grafts...
October 28, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29079181/de-novo-immune-complex-deposition-in-kidney-allografts-a-series-of-32-patients
#13
Isaac E Lloyd, Faris Ahmed, Monica P Revelo, Mazdak A Khalighi
Immune complex deposition in kidney allografts can include both recurrent and de novo processes. Recurrent glomerulonephritis is a well-recognized phenomenon and has been shown to be a common cause of allograft failure. De novo immune complex-mediated disease remains relatively poorly characterized, likely owing to the less frequent use of immunofluorescence and electron microscopy in the transplant setting. We performed a retrospective review of kidney allograft biopsies showing glomerular immune complex deposition...
October 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/29075627/characteristics-of-donor-specific-antibodies-associated-with-antibody-mediated-rejection-in-lung-transplantation
#14
Antoine Roux, Ines Bendib Le Lan, Sonia Holifanjaniaina, Kimberly A Thomas, Clément Picard, Dominique Grenet, Sandra De Miranda, Benoit Douvry, Laurence Beaumont-Azuar, Edouard Sage, Jérôme Devaquet, Elise Cuquemelle, Morgan Le Guen, Caroline Suberbielle, Chantal Gautreau, Marc Stern, Maura Rossetti, Abdul Monem Hamid, Francois Parquin
Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010-2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMR(Pos), n = 22, and AMR(Neg), n = 83, respectively) were compared...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29069327/the-role-of-complement-inhibition-in-kidney-transplantation
#15
C Legendre, R Sberro-Soussan, J Zuber, V Frémeaux-Bacchi
Introduction and background: The complement system which belongs to the innate immune system acts both as a first line of defence against various pathogens and as a guardian of host homeostasis. The role of complement has been recently highlighted in several aspects of kidney transplantation: ischaemia-reperfusion, antibody-mediated rejection and native kidney disease recurrence. Sources of data: Experimental data, availability of complement-blocking molecules (mainly the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney transplant recipients has led to some areas of agreement and some disappointment...
October 21, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29061332/human-plasmacytoid-dendritic-cells-acquire-phagocytic-capacity-by-tlr9-ligation-in-the-presence-of-soluble-factors-produced-by-renal-epithelial-cells
#16
Jurjen M Ruben, Gina Stella García-Romo, Eytan Breman, Sandra van der Kooij, Anke Redeker, Ramon Arens, Cees van Kooten
Plasmacytoid dendritic cells (pDCs) are antigen presenting cells specialized in viral recognition through Toll-like receptor (TLR)7 and TLR9, and produce vast amounts of interferon alpha upon ligation of these TLRs. We had previously demonstrated a strong influx of pDCs in the tubulointerstitium of renal biopsies at the time of acute rejection. However, the role of human pDCs in mediating acute or chronic allograft rejection remains elusive. pDCs are thought to have a limited capacity to ingest apoptotic cells, critical for inducing CD4(+) T cell activation via indirect antigen presentation and subsequent activation of antibody producing B cells...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29055600/prevalence-of-polyreactive-innate-clones-among-graft-infiltrating-b-cells-in-human-cardiac-allograft-vasculopathy
#17
Debanjana Chatterjee, Carolina Moore, Baoshan Gao, Kevin J Clerkin, Sarah B See, David Shaked, Kortney Rogers, Sarah Nunez, Yokarla Veras, Linda Addonizio, Michael M Givertz, Yoshifumi Naka, Donna Mancini, Rodica Vasilescu, Charles Marboe, Susan Restaino, Joren C Madsen, Emmanuel Zorn
BACKGROUND: Cardiac allograft vasculopathy (CAV) has been associated with graft-infiltrating B cells, although their characteristics are still unclear. In this study we examined the frequency, localization and reactivity profile of graft-infiltrating B cells to determine their contribution to the pathophysiology of CAV. METHODS: B cells, plasma cells and macrophages were examined by immunohistochemistry in 56 allografts with CAV, 49 native failed hearts and 25 autopsy specimens...
September 28, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29053910/a-simplified-protocol-using-rituximab-and-immunoglobulin-for-abo-incompatible-low-titre-living-donor-liver-transplantation
#18
Seong Hoon Kim, Eung Chang Lee, Jae Ryong Shim, Sang Jae Park
BACKGROUND & AIMS: No consensus has been reached regarding optimal treatment strategies for ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). We introduce a simplified protocol using rituximab and intravenous immunoglobulin (IVIG). METHODS: Data were analysed on adult patients who underwent ABO-I LDLT of which protocol added rituximab (300 mg/m(2) ) before surgery and IVIG (0.8 g/kg) on post-operative days 1 and 4 to the conventional immunosuppressive regimen used in ABO-compatible (ABO-C) LDLT, without plasmapheresis, splenectomy or graft local infusion...
October 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29045076/outside-in-hla-class-i-signaling-regulates-icam-1-clustering-and-endothelial-monocyte-interactions-via-mtor-in-transplant-antibody-mediated-rejection
#19
Sahar Salehi, Rebecca A Sosa, Yi-Ping Jin, Shoichi Kageyama, Michael C Fishbein, Enrique Rozengurt, Jerzy W Kupiec-Weglinski, Elaine F Reed
Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment...
October 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#20
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
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