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Transplant tolerance

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https://www.readbyqxmd.com/read/28728162/realistic-lenalidomide-dose-adjustment-strategy-for-transplant-ineligible-elderly-patients-with-relapsed-refractory-multiple-myeloma-japanese-real-world-experience
#1
Aya Nakaya, Shinya Fujita, Atsushi Satake, Takahisa Nakanishi, Yoshiko Azuma, Yukie Tsubokura, Masaaki Hotta, Hideaki Yoshimura, Kazuyoshi Ishii, Tomoki Ito, Shosaku Nomura
Lenalidomide is an immunomodulatory drug administered orally in the treatment of multiple myeloma. Some elderly patients require a reduced lenalidomide dose because of comorbidities and/or adverse events. This study investigated the actual dose of lenalidomide in elderly patients, finding that most received reduced (5-10 mg) doses. The most common reasons for dose reduction were renal dysfunction (54% of patients), fatigue (grade ≥3; 20%), hematologic disorder (grade ≥3; 14%), and rash (grade ≥3; 9%)...
July 21, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28727250/lack-of-adjustment-for-confounding-could-lead-to-misleading-conclusions
#2
EDITORIAL
S Christakoudi, M P Hernandez-Fuentes
In a recent issue Asare et al. (1) assess the utility of a previously identified signature of tolerance, based on the expression of two B-cell receptor genes (IGKV1D-13 and IGKV4-1). The authors set to determine the prevalence of "tolerance" predictions in treated stable kidney transplant recipients (KTRs) and "tolerance" frequency in patients with different immunosuppressant (IS) regimens. They illustrate (Figure 6), very successfully, that changes in the signature are compatible with known alterations of the B-cell compartment elicited by IS drugs...
July 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28724765/translesion-polymerase-pol-%C3%AE-is-required-for-efficient-epstein-barr-virus-infectivity-and-is-regulated-by-the-viral-deubiquitinating-enzyme-bplf1
#3
Ossie F Dyson, Joseph S Pagano, Christopher B Whitehurst
Epstein-Barr Virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. Previously we showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis pathway (TLS), a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument indicating that BPLF1 may function both early and late during infection. BPLF1 expresses deubiquitinating activity that is strictly conserved across the Herpesviridae; mutation of the active-site cysteine results in loss of enzymatic activity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722153/pharmacokinetics-and-safety-of-the-anti-human-cytomegalovirus-drug-letermovir-in-subjects-with-hepatic-impairment
#4
D Kropeit, D McCormick, K Erb-Zohar, V S Moiseev, Z D Kobalava, H P Stobernack, H Zimmermann, H Rübsamen-Schaeff
AIM: Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/preemptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. METHODS: Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls...
July 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28720321/no-evidence-for-progressive-deterioration-in-stimulated-insulin-secretion-in-renal-transplant-recipients-after-12years-tacrolimus-exposure
#5
Mariëlle A C J Gelens, Johannes P van Hooff, Len Usvyat, Maarten H Christiaans
AIMS: Tacrolimus (Tac) inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant in renal transplant recipients (Rtx). It is unknown whether long-term exposure results into a progressive beta cells dysfunction. METHODS: Two independent cohorts of Tac-treated non-diabetic Rtx, previously participating in glucose metabolism studies using intravenous Glucose Tolerance Test (ivGTT) were included: Fifty-eight Rtx were tested by ivGTT cross-sectional between 0...
July 4, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28719761/rehabilitation-and-postoperative-management-practices-after-osteochondral-allograft-transplants-to-the-distal-femur-a-report-from-the-metrics-of-osteochondral-allografts-moca-study-group-2016-survey
#6
Marie S Kane, Karlee Lau, Dennis C Crawford
CONTEXT: We present the current spectrum of postoperative management practices for patients receiving distal femur osteochondral allograft (OCA) transplants. EVIDENCE ACQUISITION: The Joint Restoration Foundation database was examined in cooperation with the Metrics of Osteochondral Allografts study group to identify 121 surgeons who had performed at least 1 OCA transplant in the past year; 63% of surgeons responded. STUDY DESIGN: Clinical survey...
July 1, 2017: Sports Health
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#7
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28713424/prolonged-survival-of-subcutaneous-allogeneic-islet-graft-by-donor-chimerism-without-immunosuppressive-treatment
#8
Brend Ray-Sea Hsu, Shin-Huei Fu, Aline Yen Ling Wang
The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2(b)) mice to construct donor chimerism in conditioned diabetic BALB/c (H2(d)) mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28706973/splenocyte-infusion-and-whole-body-irradiation-for-induction-of-peripheral-tolerance-in-porcine-lung-transplantation-modifications-of-the-preconditioning-regime-for-improved-clinical-feasibility
#9
Katharina Jansson, Karla Dreckmann, Wiebke Sommer, Murat Avsar, Jawad Salman, Thierry Siemeni, Ann-Kathrin Knöfel, Linda Pauksch, Jens Gottlieb, Jörg Frühauf, Martin Werner, Danny Jonigk, Martin Strüber, Axel Haverich, Gregor Warnecke
BACKGROUND: Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed. METHODS: Left-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28705305/clinical-characteristics-of-japanese-candidates-for-lung-transplant-for-interstitial-lung-disease-and-risk-factors-for-early-death-while-on-the-waiting-list
#10
Hisao Higo, Takeshi Kurosaki, Eiki Ichihara, Toshio Kubo, Kentaroh Miyoshi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Nobuaki Miyahara, Katsuyuki Kiura, Shinichiro Miyoshi, Takahiro Oto
BACKGROUND: Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. METHODS: We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015...
July 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28703287/immune-tolerance-in-transplantation
#11
EDITORIAL
Thomas Wekerle
No abstract text is available yet for this article.
August 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28702031/alloantigen-induced-regulatory-t-cells-generated-in-presence-of-vitamin-c-display-enhanced-stability-of-foxp3-expression-and-promote-skin-allograft-acceptance
#12
Eirini Nikolouli, Matthias Hardtke-Wolenski, Martin Hapke, Michael Beckstette, Robert Geffers, Stefan Floess, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, vitamin C was reported to enhance the activity of enzymes of the ten-eleven translocation family, thereby fostering the demethylation of Foxp3 and other Treg-specific epigenetic signatures genes in developing Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28700815/mesenchymal-stem-cells-and-their-immunosuppressive-role-in-transplantation-tolerance
#13
REVIEW
Pamina Contreras-Kallens, Claudia Terraza, Karina Oyarce, Tania Gajardo, Mauricio Campos-Mora, María Teresa Barroilhet, Carla Álvarez, Ricardo Fuentes, Fernando Figueroa, Maroun Khoury, Karina Pino-Lagos
Since they were first described, mesenchymal stem cells (MSCs) have been shown to have important effector mechanisms and the potential for use in cell therapy. A great deal of research has been focused on unveiling how MSCs contribute to anti-inflammatory responses, including describing several cell populations involved and identifying soluble and other effector molecules. In this review, we discuss some of the contemporary evidence for use of MSCs in the field of immune tolerance, with a special emphasis on transplantation...
July 12, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28698955/role-of-natural-igm-autoantibodies-igm-naa-and-igm-anti-leukocyte-antibodies-igm-ala-in-regulating-inflammation
#14
Peter I Lobo
Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens and abrogate inflammation mediated by invading microorganisms and host neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low binding affinity but with high avidity, characteristics that allow these antibodies to bind antigenic determinants shared by pathogens and neoantigens. Hence the same clones of natural IgM can bind and mask host neoantigens as well as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory response via mechanisms involving binding of IgM to apoptotic cells to enhance their removal and binding of IgM to live leukocytes to regulate their function...
July 12, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28698834/biomarkers-in-renal-transplantation-an-updated-review
#15
REVIEW
Maurizio Salvadori, Aris Tsalouchos
Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasive indicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment...
June 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28697925/variable-expressivity-of-a-founder-mutation-in-the-eif2ak4-gene-in-hereditary-pulmonary-veno-occlusive-disease-and-its-impact-on-survival
#16
Paula Navas Tejedor, Julián Palomino Doza, Jair Antonio Tenorio Castaño, Ana Belén Enguita Valls, José Julián Rodríguez Reguero, Amaya Martínez Meñaca, Ignacio Hernández González, Héctor Bueno Zamora, Pablo Daniel Lapunzina Badía, Pilar Escribano Subías
INTRODUCTION AND OBJECTIVES: Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course...
July 8, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28695649/single-center-experience-of-antifungal-prophylaxis-for-coccidioidomycosis-in-heart-transplant-recipients-within-an-endemic-area
#17
Graham M Lohrmann, Darko Vucicevic, Romy Lawrence, D Eric Steidley, Robert L Scott, Shimon Kusne, Janis E Blair
In endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174-person cohort all received antifungal prophylaxis for at least 6 months (mean follow-up, 53...
July 11, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28695288/introduction-mhc-kir-and-governance-of-specificity
#18
REVIEW
Adrian Kelly, John Trowsdale
The MHC controls specificity, to ensure that appropriate immune responses are mounted to invading pathogens whilst maintaining tolerance to the host. It encodes molecules that act as sentinels, providing a snapshot of the health of the interior and exterior of the cell for immune surveillance. To maintain the ability to respond appropriately to any disease requires a delicate balance of expression and function, and many subtleties of the system have been described at the gene, individual and population level...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28694031/in-vivo-induction-of-regulatory-t-cells-promotes-allergen-tolerance-and-suppresses-allergic-contact-dermatitis
#19
Stephen C Balmert, Cara Donahue, John R Vu, Geza Erdos, Louis D Falo, Steven R Little
Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin condition, characterized by an intensely pruritic rash at the site of contact with allergens like poison ivy or nickel. Current clinical treatments use topical corticosteroids, which broadly and transiently suppress inflammation and symptoms of ACD, but fail to address the underlying immune dysfunction. Here, we present an alternative therapeutic approach that teaches the immune system to tolerate contact allergens by expanding populations of naturally suppressive allergen-specific regulatory T cells (Tregs)...
July 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28692527/sildenafil-in-left-ventricular-assist-device-is-safe-and-well-tolerated
#20
Ashwin K Ravichandran, Shane J LaRue, Eric Novak, Susan A Joseph, Joel D Schilling
Right heart failure is a potentially devastating complication of mechanical circulatory support, occurring at a rate of 0.49 events per 100 patient-months. Pulmonary vasodilators such as phosphodiesterase-5 inhibitors (PDE5i) have been frequently used to unload the right ventricle in left ventricular assist device (LVAD) patients, but there is scant evidence to support this practice. The purpose of this analysis is to provide additional data regarding the safety and efficacy of the PDE5i sildenafil in a real world population of patients supported with LVADs at Washington University in St...
July 7, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
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