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Humoral rejection

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https://www.readbyqxmd.com/read/29225601/anti-donor-immune-responses-elicited-by-allogeneic-mesenchymal-stem-cells-and-their-extracellular-vesicles-are-we-still-learning
#1
REVIEW
Paul Lohan, Oliver Treacy, Matthew D Griffin, Thomas Ritter, Aideen E Ryan
Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous) MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29218052/spoiling-for-a-fight-b-lymphocytes-as-initiator-and-effector-populations-within-tertiary-lymphoid-organs-in-autoimmunity-and-transplantation
#2
REVIEW
Jawaher Alsughayyir, Gavin J Pettigrew, Reza Motallebzadeh
Tertiary lymphoid organs (TLOs) develop at ectopic sites within chronically inflamed tissues, such as in autoimmunity and rejecting organ allografts. TLOs differ structurally from canonical secondary lymphoid organs (SLOs), in that they lack a mantle zone and are not encapsulated, suggesting that they may provide unique immune function. A notable feature of TLOs is the frequent presence of structures typical of germinal centers (GCs). However, little is known about the role of such GCs, and in particular, it is not clear if the B cell response within is autonomous, or whether it synergizes with concurrent responses in SLOs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29215459/complete-b-cell-deficiency-reduces-allograft-inflammation-and-intragraft-macrophages-a-rat-kidney-transplant-model
#3
Sarah E Panzer, Nancy A Wilson, Bret M Verhoven, Ding Xiang, C Dustin Rubinstein, Robert R Redfield, Weixiong Zhong, Shannon R Reese
BACKGROUND: Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. METHODS: To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B) or wild type Lewis recipients...
December 5, 2017: Transplantation
https://www.readbyqxmd.com/read/29210728/are-donor-lymphocytes-a-barrier-to-transplantation-tolerance
#4
Jawaher Alsughayyir, Reza Motallebzadeh, Gavin J Pettigrew
PURPOSE OF REVIEW: Following solid organ transplantation (SOT), populations of donor lymphocytes are frequently found in the recipient circulation. Their impact on host alloimmunity has long been debated but remains unclear, and it has been suggested that transferred donor lymphocytes may either promote tolerance to the graft or hasten its rejection. We discuss possible mechanisms by which the interaction of donor passenger lymphocytes with recipient immune cells may either augment the host alloimmune response or inhibit it...
November 27, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29202467/endothelial-chimerism-and-vascular-sequestration-protect-pancreatic-islet-grafts-from-antibody-mediated-rejection
#5
Chien-Chia Chen, Eric Pouliquen, Alexis Broisat, Francesco Andreata, Maud Racapé, Patrick Bruneval, Laurence Kessler, Mitra Ahmadi, Sandrine Bacot, Carole Saison-Delaplace, Marina Marcaud, Jean-Paul Duong Van Huyen, Alexandre Loupy, Jean Villard, Sandrine Demuylder-Mischler, Thierry Berney, Emmanuel Morelon, Meng-Kun Tsai, Marie-Nathalie Kolopp-Sarda, Alice Koenig, Virginie Mathias, Stéphanie Ducreux, Catherine Ghezzi, Valerie Dubois, Antonino Nicoletti, Thierry Defrance, Olivier Thaunat
Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models...
November 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29194971/the-causes-significance-and-consequences-of-inflammatory-fibrosis-in-kidney-transplantation-the-banff-i-ifta-lesion
#6
Brian J Nankivell, Meena Shingde, Karen L Keung, Caroline L-S Fung, Richard J Borrows, Philip J O'Connell, Jeremy R Chapman
Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation. We evaluated i-IFTA in 429 indication- and 2052 protocol-biopsies from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time-course, and relationships with T cell mediated rejection (TCMR), immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation, and followed by IF/TA...
December 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29163552/t-follicular-helper-cells-as-a-new-target-for-immunosuppressive-therapies
#7
REVIEW
Lin Yan, Kitty de Leur, Rudi W Hendriks, Luc J W van der Laan, Yunying Shi, Lanlan Wang, Carla C Baan
Over the past decade, antibody-mediated (humoral) rejection has been recognized as a common cause of graft dysfunction after organ transplantation and an important determinant for graft loss. In humoral alloimmunity, T follicular helper (Tfh) cells play a crucial role, because they help naïve B cells to differentiate into memory B cells and alloantibody-producing plasma cells within germinal centers. In this way, they contribute to the induction of donor-specific antibodies, which are responsible for the humoral immune response to the allograft...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29160947/thymic-function-is-a-major-determinant-of-antibody-mediated-rejection-onset-in-heart-transplantation
#8
A Sannier, N Stroumza, G Caligiuri, M Le Borgne-Moynier, F Andreata, J Senemaud, L Louedec, G Even, A T Gaston, C Deschildre, A Couvelard, P Ou, R Cheynier, P Nataf, R Dorent, A Nicoletti
Thymic function progressively decreases with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether the thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects...
November 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29146891/heart-transplantation-and-risk-of-cardiac-vasculopathy-development-what-factors-are-important
#9
Małgorzata Sobieszczańska-Małek, Jerzy Korewicki, Krzysztof Komuda, Małgorzata Karczmarz, Sylwia Szymańska, Alicja Cicha-Mikołajczyk, Paweł Bekta, Adam Parulski, Maciej Pronicki, Wiesława Grajkowska, Grzegorz Małek, Przemysław Leszek, Maria Kaczorowska, Mariusz Kuśmierczyk, Tomasz Zieliński
BACKGROUND The aim of this study was to find the main risk factors for development of cardiac allograft vasculopathy (CAV), especially factors identified before the surgical procedure and factors related to the recipient profile and the medical history of the donor. MATERIAL AND METHODS There were 147 patients who had heart transplantation (HT) included in this study: mean age was 45.8±15.3 years. All study patients had coronary angiography after HT. Analyzed risk factors were: non-immunologic recipient risk factors (age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT), immunologic recipient risk factors (acute cellular rejection (ACR), acute humoral rejection (AMR), cytomegalovirus (CMV) episodes), and donor-related risk factors (age, sex, catecholamine usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest)...
November 17, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29128017/acute-rejection-and-antibody-mediated-rejection-in-lung-transplantation
#10
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/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/29057510/release-of-pig-leukocytes-and-reduced-human-nk-cell-recruitment-during-ex-vivo-perfusion-of-hla-e-human-cd46-double-transgenic-pig-limbs-with-human-blood
#12
Gisella Puga Yung, Anjan K Bongoni, Amandine Pradier, Natacha Madelon, Maria Papaserafeim, Riccardo Sfriso, David L Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Bähr, Mihai A Constantinescu, Esther Voegelin, David Kiermeir, Hansjörg Jenni, Robert Rieben, Jörg D Seebach
BACKGROUND: In pig-to-human xenotransplantation, interactions between human natural killer (NK) cells and porcine endothelial cells (pEC) are characterized by recruitment and cytotoxicity. Protection from xenogeneic NK cytotoxicity can be achieved in vitro by the expression of the non-classical human leukocyte antigen-E (HLA-E) on pEC. Thus, the aim of this study was to analyze NK cell responses to vascularized xenografts using an ex vivo perfusion system of pig limbs with human blood...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29024716/accelerated-humoral-renal-allograft-rejection-due-to-hla-c14-mediated-allosensitization-to-hla-bw6
#13
Stephen P Persaud, Brian Duffy, Donna L Phelan, Thalachallour Mohanakumar, Rowena Delos Santos, Joseph P Gaut, Chang Liu
OBJECTIVES: To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera. METHODS: Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods...
October 9, 2017: Human Immunology
https://www.readbyqxmd.com/read/28946961/secondary-thrombotic-microangiopathy-and-eculizumab-a-reasonable-therapeutic-option
#14
Elena Román, Santiago Mendizábal, Isidro Jarque, Javier de la Rubia, Amparo Sempere, Enrique Morales, Manuel Praga, Ana Ávila, José Luis Górriz
Understanding the role of the complement system in the pathogenesis of atypical haemolytic uraemic syndrome and other thrombotic microangiopathies (TMA) has led to the use of anti-complement therapy with eculizumab in these diseases, in addition to its original use in patients with paroxysmal nocturnal haemoglobinuria andatypical haemolytic uraemic syndrome. Scientific evidence shows that both primary and secondary TMAs with underlying complement activation are closely related. For this reasons, control over the complement system is a therapeutic target...
September 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28929088/microbial-invasion-vs-tick-immune-regulation
#15
REVIEW
Daniel E Sonenshine, Kevin R Macaluso
Ticks transmit a greater variety of pathogenic agents that cause disease in humans and animals than any other haematophagous arthropod, including Lyme disease, Rocky Mountain spotted fever, human granulocytic anaplasmosis, babesiosis, tick-borne encephalitis, Crimean Congo haemorhagic fever, and many others (Gulia-Nuss et al., 2016). Although diverse explanations have been proposed to explain their remarkable vectorial capacity, among the most important are their blood feeding habit, their long term off-host survival, the diverse array of bioactive molecules that disrupt the host's natural hemostatic mechanisms, facilitate blood flow, pain inhibitors, and minimize inflammation to prevent immune rejection (Hajdušek et al...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28916402/the-mechanisms-of-rejection-in-solid-organ-transplantation
#16
REVIEW
Emanuele Cozzi, Anna Colpo, Giustina De Silvestro
Organ transplantation represents the preferred treatment option for many patients in terminal organ failure. The half-life of transplanted organs, however, is still far from being satisfactory with the vast majority of the organs failing within the first two decades following transplantation. At this stage, it has become apparent that rejection (prevalently mediated by humoral events) remains the primary cause of graft loss after the first year. In this light, studies are underway to better comprehend the immune events underlying graft rejection and novel immunosuppressive strategies are being explored...
July 8, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28894277/host-expression-of-the-cd8-treg-nk-cell-restriction-element-qa-1-is-dispensable-for-transplant-tolerance
#17
Blair T Stocks, Christopher S Wilson, Andrew F Marshall, Lauren A Brewer, Daniel J Moore
Disruption of the non-classical Major Histocompatibility Complex (MHC) Ib molecule Qa-1 impairs CD8 Treg and natural killer (NK) cell function and promotes a lupus-like autoimmune disease. This immune perturbation would be expected to enhance anti-transplant responses and impair tolerance induction, but the effect of Qa-1 deficiency on the transplant response has not been previously reported. Qa-1 deficiency enhanced CD4 TFH and germinal center (GC) B cell numbers in naïve mice and hastened islet allograft rejection...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894081/eculizumab-in-renal-transplantation-a-2017-update
#18
Ryszard Grenda, Magdalena Durlik
Despite ongoing progress in renal transplantation, there are still emerging challenges in this field, including consequences of ischemia-reperfusion injury (IRI), pre-existing and produced de novo anti-HLA donor-specific antibodies (DSA), and acute/chronic humoral rejection (AMR), as well as the recurrence of atypical hemolytic-uremic syndrome (aHUS) in genetically predisposed patients. All these conditions are related to the prominent role of the complement system and are deleterious to the fate of the renal graft...
September 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28808594/spontaneous-renal-allograft-rupture-caused-by-acute-tubular-necrosis-a-case-report-and-review-of-the-literature
#19
Deepak Shankar Ray, Sharmila Thukral
Renal allograft rupture (RAR) is a rare but lethal complication of renal transplantation. It potentially threatens graft and patient survival. RAR is frequently associated with acute rejection, but other causes like renal vein thrombosis and acute tubular necrosis have also been observed. Most commonly a graft nephrectomy is required, but graft repair can also be attempted in selected cases to salvage the graft. Herein, we describe a rare case of spontaneous renal allograft rupture in the early posttransplant period due to acute tubular necrosis...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28783665/structural-basis-for-potent-antibody-mediated-neutralization-of-human-cytomegalovirus
#20
Sumana Chandramouli, Enrico Malito, TuongVi Nguyen, Kate Luisi, Danilo Donnarumma, Yi Xing, Nathalie Norais, Dong Yu, Andrea Carfi
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A...
June 30, 2017: Science Immunology
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