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tolerance in transplantation

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https://www.readbyqxmd.com/read/28106077/mesenchymal-stem-cell-transplantation-in-tight-skin-mice-identifies-mir-151-5p-as-a-therapeutic-target-for-systemic-sclerosis
#1
Chider Chen, Dandan Wang, Alireza Moshaverinia, Dawei Liu, Xiaoxing Kou, Wenjing Yu, Ruili Yang, Lingyun Sun, Songtao Shi
Systemic sclerosis (SSc), an autoimmune disease, may cause significant osteopenia due to activation of the IL4Rα/mTOR pathway. Mesenchymal stem cell transplantation (MSCT) can ameliorate immune disorders in SSc via inducing immune tolerance. However, it is unknown whether MSCT rescues osteopenia phenotype in SSc. Here we show that MSCT can effectively ameliorate osteopenia in SSc mice by rescuing impaired lineage differentiation of the recipient bone marrow MSCs. Mechanistically, we show that donor MSCs transfer miR-151-5p to the recipient bone marrow MSCs in SSc mice to inhibit IL4Rα expression, thus downregulating mTOR pathway activation to enhance osteogenic differentiation and reduce adipogenic differentiation...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#2
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of GVHD after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
January 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28104136/acute-calcineurin-inhibitor-nephrotoxicity-secondary-to-turmeric-intake-a-case-report
#3
A Nayeri, S Wu, E Adams, C Tanner, J Meshman, I Saini, W Reid
Tacrolimus, also known as FK-506, is a potent immunosuppressant agent with a host of drug-drug and food-drug interactions. We present the first case of a probable food-drug interaction between the herb turmeric and tacrolimus leading to acute calcineurin inhibitor nephrotoxicity. A 56-year-old man with a history of orthotopic liver transplantation presented to the emergency department from the clinic with worsening edema in the setting of an elevated creatinine level of 4.2 mg/dL. Before the current presentation, the patient had been recently discharged on a previously tolerated low-dose regimen of tacrolimus with a whole-blood tacrolimus level within the desired range...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28102293/ocean-warming-and-acidification-synergistically-increase-coral-mortality
#4
F Prada, E Caroselli, S Mengoli, L Brizi, P Fantazzini, B Capaccioni, L Pasquini, K E Fabricius, Z Dubinsky, G Falini, S Goffredo
Organisms that accumulate calcium carbonate structures are particularly vulnerable to ocean warming (OW) and ocean acidification (OA), potentially reducing the socioeconomic benefits of ecosystems reliant on these taxa. Since rising atmospheric CO2 is responsible for global warming and increasing ocean acidity, to correctly predict how OW and OA will affect marine organisms, their possible interactive effects must be assessed. Here we investigate, in the field, the combined temperature (range: 16-26 °C) and acidification (range: pHTS 8...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102024/generating-antigen-specific-regulatory-t-cells-in-the-fast-lane
#5
EDITORIAL
Leonardo M R Ferreira, Qizhi Tang
Since the inception of therapeutic allogeneic transplantation, acceptance of transplanted allografts has depended on non-specific immunosuppression, which blunts the recipient's immune defense yet cannot fully prevent chronic rejection. What if one could induce tolerance specifically to the graft? This article is protected by copyright. All rights reserved.
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28101345/%C3%AE-cell-function-prior-to-liver-transplantation-contributes-to-post-operative-diabetes
#6
Tatsuki Ichikawa, Naota Taura, Hisamitsu Miyaaki, Satoshi Miuma, Hidetaka Shibata, Takuya Honda, Masaaki Hidaka, Akihiko Soyama, Mitsuhisa Takatsuki, Susumu Eguchi, Kazuhiko Nakao
Liver cirrhosis and diabetes mellitus (DM) are closely associated. The present study aimed to determine whether liver transplantation (LT) may prevent/cure DM in patients with cirrhosis and whether the degree of glucose tolerance prior to transplantation is associated with the onset of DM after transplantation. Seventy-three patients who received a living donor LT at Nagasaki University Hospital (Nagasaki, Japan) between November 2005 and December 2012 were recruited. Among them, patients were considered diabetic if they had been prescribed diabetes medications or had impaired glucose tolerance, as evidenced by an oral glucose tolerance test (OGTT)...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#7
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#8
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#9
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096089/tolerogenic-interactions-between-cd8-dendritic-cells-and-nkt-cells-prevent-rejection-of-bone-marrow-and-organ-grafts
#10
David Hongo, Xiaobin Tang, Xiangyue Zhang, Edgar G Engleman, Samuel Strober
The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095640/irradiation-before-and-donor-splenocyte-infusion-immediately-after-transplantation-induce-tolerance-to-lung-but-not-heart-allografts-in-miniature-swine
#11
Wiebke Sommer, Gwen Buechler, Katharina Jansson, Murat Avsar, Ann-Kathrin Knöfel, Jawad Salman, Klaus Hoeffler, Thierry Siemeni, Jens Gottlieb, Johann H Karstens, Danny Jonigk, Ansgar Reising, Axel Haverich, Martin Strüber, Gregor Warnecke
Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four, and left-sided lung transplantation (LTX) in seven minipigs from gender and SLA mismatched donors. All recipients received non-myeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days...
January 17, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28093339/short-term-clinical-safety-profile-of-brincidofovir-a-favorable-benefit-risk-proposition-in-the-treatment-of-smallpox
#12
Greg Chittick, Marion Morrison, Thomas Brundage, W Garrett Nichols
Brincidofovir (BCV, CMX001) is an orally available, long-acting, broad-spectrum antiviral that has been evaluated in healthy subjects in Phase I studies and in hematopoietic cell transplant recipients and other immunocompromised patients in Phase II/III clinical trials for the prevention and treatment of cytomegalovirus and adenovirus infections. BCV has also shown in vitro activity against orthopoxviruses such as variola (smallpox) virus, and is under advanced development as a treatment for smallpox under the US FDA's 'Animal Rule'...
January 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28092129/bortezomib-in-the-treatment-of-antibody-mediated-rejection-in-pediatric-kidney-transplant-recipients-a-multicenter-midwest-pediatric-nephrology-consortium-study
#13
Sarah Kizilbash, Donna Claes, Isa Ashoor, Ashton Chen, Sara Jandeska, Raed Bou Matar, Jason Misurac, Joseph Sherbotie, Katherine Twombley, Priya Verghese
Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients...
January 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28088971/-eltrombopag-for-refractory-thrombocytopenia-in-patients-with-allogeneic-hematopoietic-stem-cell-transplantation
#14
Y R Ma, X J Huang, X D Mo, W Han, C H Yan, Y Chen, Y Ji, Y Y Chen, Y Wang, X H Zhang, K Y Liu, L P Xu
Objective: To evaluate the efficacy and safety of eltrombopag in post-HSCT thrombocytopenia. Methods: A total of 10 patients who underwent post-HSCT thrombocytopenia at Peking University center, who had been treated with eltrombopag, were retrospectively evaluated. Results: Of the 10 cases, 5 males and 5 females with a median of 34 years old (range, 17-54 years), 5 patients were acute myeloid leukemia, 3 with acute lymphoid leukemia and 2 with severe aplastic anemia. Nine patients had undergone haplo-identical donor transplantation, and one patient was a matched related recipient...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#15
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088775/diagnostic-accuracy-of-glycated-hemoglobin-for-post-transplantation-diabetes-mellitus-after-kidney-transplantation-systematic-review-and-meta-analysis
#16
Ana Laura Pimentel, Gabriela Cavagnolli, Joíza Lins Camargo
BACKGROUND: Early detection of post-transplantation diabetes mellitus (PTDM) allows prompt clinical and pharmacological interventions, reducing the chance of adverse outcomes. We conducted a systematic review and meta-analysis to determine the overall diagnostic accuracy of glycated hemoglobin (HbA1c) for the diagnosis of renal PTDM. METHODS: We searched MEDLINE, Embase and SCOPUS up to June 2016. Studies that included adults without previous diabetes were selected if they reported an oral glucose tolerance test as a reference test, HbA1c levels measured by standardized methods and data necessary for drawing 2 × 2 tables...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28087456/phase-i-trial-of-total-marrow-and-lymphoid-irradiation-transplant-conditioning-in-patients-with-relapsed-refractory-acute-leukemia
#17
Anthony Stein, Joycelynne Palmer, Ni-Chun Tsai, Monzr M Al Malki, Ibrahim Aldoss, Haris Ali, Ahmed Aribi, Len Farol, Chatchada Karanes, Samer Khaled, An Liu, Margaret O'Donnell, Pablo Parker, Anna Pawlowska, Vinod Pullarkat, Eric Radany, Joseph Rosenthal, Firoozeh Sahebi, Amandeep Salhotra, James F Sanchez, Tim Schultheiss, Ricardo Spielberger, Sandra H Thomas, David Snyder, Ryotaro Nakamura, Guido Marcucci, Stephen J Forman, Jeffrey Wong
Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia (AL) patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28086849/successful-outcome-following-pneumonectomy-in-a-teenage-boy-with-cystic-fibrosis-a-case-report
#18
Zheyi Liew, Santosh Mallikarjuna, Asif Hasan, F Kate Gould, Su Bunn, Matthew F Thomas, Jim L Lordan, Christopher O'Brien, Malcolm Brodlie
BACKGROUND: Cystic fibrosis lung disease is generally a diffuse process however rarely one lung may become particularly damaged through chronic collapse and consolidation resulting in end-stage bronchiectasis with relative sparing of the contralateral lung. This clinical situation is sometimes referred to as "destroyed lung". Lung resection surgery is seldom indicated in cystic fibrosis and the associated medical literature is relatively sparse. CASE PRESENTATION: A 14 year old boy was referred to our centre for lung transplantation assessment...
January 13, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#19
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28077266/asp0028-in-combination-with-suboptimal-dose-of-tacrolimus-in-cynomolgus-monkey-renal-transplantation-model
#20
Hao Dun, Lijun Song, Anlun Ma, Yanxin Hu, Lin Zeng, Jieying Bai, Guangzhou Zhang, Liangyan Zhang, Kumi Koide, Yohei Okada, Kaori Hanaoka, Rie Yamamoto, Jun Hirose, Tatsuaki Morokata, Pierre Daloze, Huifang Chen
FTY720, a S1P-receptor modulator, has shown to be effective in several transplant and autoimmune disease models, via modulating lymphocyte homing into secondary lymphoid organs (SLOs), and thereby reducing these cells in peripheral blood. ASP0028, a newly developed S1P1/S1P5-selective agonist, presented comparable efficacy to FTY720 and wider safety margins than FTY720. In this study, we assessed the efficacy and safety of ASP0028 co-administered with suboptimal-dose of tacrolimus in the Cynomolgus monkey renal transplantation model...
January 7, 2017: Transplant Immunology
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