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Transplant tolerance

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https://www.readbyqxmd.com/read/29458071/b-cells-in-operational-tolerance
#1
REVIEW
M Chesneau, R Danger, J-P Soulillou, S Brouard
Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunossuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal...
February 16, 2018: Human Immunology
https://www.readbyqxmd.com/read/29457839/brincidofovir-as-salvage-therapy-for-adenovirus-disease-in-intestinal-transplant-recipients
#2
Nimisha Sulejmani, Shunji Nagai, Mohamed Safwan, Michael D Rizzari, Mohammad Raoufi, Marwan S Abouljoud, Mayur Ramesh
Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or United States Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy...
February 19, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29456655/effect-of-immune-tolerance-induced-by-immature-dendritic-cells-and-ctla4-ig-on-systemic-lupus-erythematosus-an-in-vivo-study
#3
Cuili Huang, Lidan Zhang, Fang Ling, Sijian Wen, Yanyan Luo, Hui Liu, Jingping Liu, Wenjun Zheng, Ming Liang, Jian Sun, You-Kun Lin
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29455908/increased-degradation-of-atp-is-driven-by-memory-regulatory-t-cells-in-kidney-transplantation-tolerance
#4
Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process...
February 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29451946/first-experience-in-switzerland-in-phe508del-homozygous-cystic-fibrosis-patients-with-end-stage-pulmonary-disease-enrolled-in-a-lumacaftor-ivacaftor-therapy-trial-preliminary-results
#5
Christian Murer, Lars Christian Huber, Thomas Kurowski, Astrid Hirt, Cécile A Robinson, Urs Bürgi, Christian Benden
AIMS OF THE STUDY: Cystic fibrosis is the most common genetic disorder in Caucasians. The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 <40% predicted were excluded from studies. We used LUM/IVA on a "compassionate use" basis in cystic fibrosis patients with end-stage pulmonary disease...
February 16, 2018: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29450893/dofetilide-for-suppression-of-atrial-fibrillation-in-hypertrophic-cardiomyopathy-a-case-series-and-literature-review
#6
JoEllyn C Moore, Lena Trager, Lucille E Anzia, Walid Saliba, Mohamed Bassiouny, Mandeep Bhargava, Mina Chung, Milind Desai, Ross Garberich, Harry Lever, Bruce D Lindsay, Jay Sengupta, Patrick Tchou, Oussama Wazni, Bruce L Wilkoff
BACKGROUND: Limited medical options are available for rhythm control in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). There are no published reports of dofetilide use in this population. METHODS: A retrospective chart review was conducted on1,404 patients loaded on dofetilide for AF suppression at the Cleveland Clinic from 2008-2012, 25 of whom were found to have HCM. RESULTS: The HCM cohort was 32% female, 76% with persistent AF, mean age of 59 ± 10 years and mean ejection fraction (EF) of 54 ± 9 %...
February 16, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29448053/biomarkers-of-operational-tolerance-following-kidney-transplantation-the-immune-tolerance-network-studies-of-spontaneously-tolerant-kidney-transplant-recipients
#7
REVIEW
Kenneth A Newell, Andrew B Adams, Laurence A Turka
Studies of kidney transplant recipients who have developed spontaneous and sustained tolerance have revealed an association with B cells. Unexpectedly tolerant individuals are characterized by increased numbers and frequencies of B cells in the blood and increased expression of genes associated with B cells in the blood and urine. Comparisons of the B cell repertoires of tolerant individuals and those receiving immunosuppression reveal that not only are the B cells more numerous but developmental differences result in a repertoire comprised of more naïve and transitional B cells in the tolerant cohort...
February 12, 2018: Human Immunology
https://www.readbyqxmd.com/read/29446735/epigenetic-regulation-of-regulatory-t-cells-in-kidney-disease-and-transplantation
#8
Yufeng Liu, Bo Peng, Shengdi Wu, Nuo Xu
Regulatory T (Treg) cells are a kind of immunosuppression cells, which have been used to treat autoimmune diseases and induce allograft tolerance in clinical trials. While Treg cells based therapy is a promising treatment for kidney diseases and an emerging concept for tolerance induction in renal transplantation, a better understanding of the functions and biology of Treg cells is needed to be able to optimally exploit them. Epigenetics regulation, which refers to potentially heritable alterations in gene expression without underlying changes of the nucleotide sequence, plays an important role in Treg cells induction and maintenance...
February 13, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29446001/canakinumab-treatment-in-renal-transplant-recipients-with-familial-mediterranean-fever
#9
Tolga Yildirim, Rahmi Yilmaz, Muge Uzerk Kibar, Yunus Erdem
Colchicine is the first-line treatment for familial Mediterranean fever (FMF), preventing both inflammatory attacks as well as the development of amyloidosis in the majority of the patients. However approximately 5-10% of patients are colchicine resistant/intolerant. Side effects of colchicine are more prominent in renal transplant recipients due to interaction with immunosuppressive drugs. Anti-interleukin (IL)-1 drugs (anakinra, canakinumab and rilonacept) have emerged as the most promising drugs in the treatment of colchicine-resistant and/or intolerant FMF...
February 14, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29445872/bowman-layer-transplantation-5-year-results
#10
Korine van Dijk, Jack S Parker, Lamis Baydoun, Abbas Ilyas, Isabel Dapena, Esther A Groeneveld-van Beek, Gerrit R J Melles
PURPOSE: The purpose of this study was to evaluate the 5-year clinical results of isolated Bowman layer (BL) transplantation in the treatment of advanced keratoconus. METHODS: In this prospective, single-center, interventional case series at a tertiary referral center, 20 eyes of 17 patients with advanced keratoconus underwent BL transplantation, i.e. an isolated Bowman layer graft was positioned into a manually dissected mid-stromal pocket. Scheimpflug-based corneal tomography measurements, best corrected spectacle and contact lens visual acuities (BSCVA and BCLVA), endothelial cell density, and complications were evaluated up to 5 years after surgery...
February 14, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29445104/genetic-modification-to-induce-cxcr2-overexpression-in-mesenchymal-stem-cells-enhances-treatment-benefits-in-radiation-induced-oral-mucositis
#11
Zongshan Shen, Jiancheng Wang, Qiting Huang, Yue Shi, Zhewei Wei, Xiaoran Zhang, Yuan Qiu, Min Zhang, Yi Wang, Wei Qin, Shuheng Huang, Yinong Huang, Xin Liu, Kai Xia, Xinchun Zhang, Zhengmei Lin
Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#12
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444715/porcine-wharton-s-jelly-cells-distribute-throughout-the-body-after-intraperitoneal-injection
#13
Kreeson Packthongsuk, Theresa Rathbun, Deryl Troyer, Duane L Davis
BACKGROUND: Wharton's jelly cells (WJCs) have multiple differentiation potentials and are easily harvested in large numbers. WJCs are well tolerated in allogeneic environments and there is a growing list of their therapeutic effects. Most therapies require administering large numbers of cells and this is generally accomplished by intravenous injection. Here, we studied the locations of porcine WJCs in immune-competent, allogeneic hosts after intraperitoneal (IP) injection. METHODS: Male porcine WJCs were administered to female neonatal piglets by IP injection...
February 14, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29440559/botulinum-toxin-a-increases-allograft-tolerance-in-an-experimental-transplantation-model-a-preliminary-study
#14
Yun Joo Park, Jang Won Lee, Yosep Chong, Tae Hwan Park
Identifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries. Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model.Twenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A  or with normal saline...
February 13, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29437593/%C3%AE-1-antitrypsin-infusion-for-treatment-of-steroid-resistant-acute-graft-versus-host-disease
#15
John M Magenau, Steven C Goldstein, Dan Peltier, Robert J Soiffer, Thomas Braun, Attaphol Pawarode, Mary M Riwes, Maggi Kennel, Joseph H Antin, Corey S Cutler, Vincent T Ho, Edwin P Alyea, Brian L Parkin, Gregory A Yanik, Sung Won Choi, Eli C Lewis, Charles A Dinarello, John Koreth, Pavan Reddy
Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells...
February 2, 2018: Blood
https://www.readbyqxmd.com/read/29432302/allogeneic-matched-related-donor-bone-marrow-transplantation-for-pediatric-patients-with-severe-aplastic-anemia-using-low-dose-cyclophosphamide-atg-plus-fludarabine
#16
Chayamon Takpradit, Susan E Prockop, Nancy A Kernan, Andromachi Scaradavou, Kevin Curran, Julianne Ruggiero, Nicole Zakak, Richard J O'Reilly, Farid Boulad
BACKGROUND: The combination of cyclophosphamide (CY) and antithymocyte globulin (ATG) has been used as a standard conditioning regimen for matched related donor transplantation in patients with severe aplastic anemia. PROCEDURE: To decrease the regimen-related toxicity while maintaining appropriate engraftment and survival rates, fludarabine (FLU) was added to the regimen. Four pediatric patients received matched related donor bone marrow transplantation with CY (50 mg/kg×2) (instead of the 50 mg/kg×4 standard dosing), equine ATG (30 mg/kg×3), with the addition of FLU (30 mg/m×4)...
February 9, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29432257/progression-of-living-liver-donation-worldwide
#17
Trevor L Nydam, Mettu Srinivas Reddy, Elizabeth A Pomfret, Mohamed Rela
PURPOSE OF REVIEW: Living donor liver transplantation (LDLT) has developed into a well tolerated and viable option when deceased donor transplantation is not available. Transplant and advanced hepatobiliary surgeons from around the world have performed living donor hepatectomies consistently for decades with acceptable donor outcomes. However, optimizing the preoperative workup, donor selection, operative technique, and perioperative care will improve these outcomes. This manuscript reviews recent worldwide literature for the living liver donor...
February 9, 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29431690/ildr2-fc-is-a-novel-regulator-of-immune-homeostasis-and-inducer-of-antigen-specific-immune-tolerance
#18
Joseph R Podojil, Iris Hecht, Ming-Yi Chiang, Ilan Vaknin, Inbal Barbiro, Amit Novik, Eyal Neria, Galit Rotman, Stephen D Miller
ILDR2 is a member of the Ig superfamily, which is implicated in tricellular tight junctions, and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. In this article, we show that short-term treatment with ILDR2-Fc results in long-term durable beneficial effects in the relapsing-remitting experimental autoimmune encephalomyelitis and NOD type 1 diabetes models. ILDR2-Fc also promotes transplant engraftment in a minor mismatch bone marrow transplantation model...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29427591/steroid-regulation-an-overlooked-aspect-of-tolerance-and-chronic-rejection-in-kidney-transplantation
#19
Sofia Christakoudi, Manohursingh Runglall, Paula Mobillo, Irene Rebollo-Mesa, Tjir-Li Tsui, Estefania Nova-Lamperti, Sonia Norris, Yogesh Kamra, Rachel Hilton
Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared...
February 7, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29425206/genome-wide-association-study-to-identify-candidate-loci-and-genes-for-mn-toxicity-tolerance-in-rice
#20
Asis Shrestha, Ambrose Kwaku Dziwornu, Yoshiaki Ueda, Lin-Bo Wu, Boby Mathew, Michael Frei
Manganese (Mn) is an essential micro-nutrient for plants, but flooded rice fields can accumulate high levels of Mn2+ leading to Mn toxicity. Here, we present a genome-wide association study (GWAS) to identify candidate loci conferring Mn toxicity tolerance in rice (Oryza sativa L.). A diversity panel of 288 genotypes was grown in hydroponic solutions in a greenhouse under optimal and toxic Mn concentrations. We applied a Mn toxicity treatment (5 ppm Mn2+, 3 weeks) at twelve days after transplanting. Mn toxicity caused moderate damage in rice in terms of biomass loss and symptom formation despite extremely high shoot Mn concentrations ranging from 2...
2018: PloS One
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