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tolerance in transplantation

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https://www.readbyqxmd.com/read/28736013/outcomes-of-highly-sensitized-patients-undergoing-simultaneous-liver-and-kidney-transplantation-a-single-center-experience-with-desensitization
#1
J A Steggerda, A Kang, S-H Pan, V Sundaram, N N Nissen, A S Klein, T Todo, A Annamalai, A Vo, S C Jordan, I K Kim
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28734876/t-cell-depletion-as-an-alternative-approach-for-patients-55-years-undergoing-allogeneic-stem-cell-transplantation-as-curative-therapy-for-hematologic-malignancies
#2
Ann A Jakubowski, Erica Petrlik, Molly Maloy, Patrick Hilden, Esperanza Papadopoulos, James W Young, Farid Boulad, Hugo Castro-Malaspina, Roni Tamari, Parastoo B Dahi, Jenna Goldberg, Guenther Koehne, Miguel-Angel Perales, Craig S Sauter, Richard J O'Reilly, Sergio Giralt
T cell depleted allogeneic hematopoietic stem cell transplantation (TCD HSCT) is curative treatment for hematologic malignancies in adults, shown to reduce graft vs. host disease (GVHD) without increased relapse. We retrospectively reviewed a single center, 11yr experience of 214 patients ≥55yrs to determine tolerability and efficacy in the older adult. The majority (70%) had myeloid diseases and most acute leukemias were in remission. Median age was 61 yrs with related and unrelated donors > 8/10 HLA matched...
July 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#3
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730633/pd-1-expression-on-cd8-t-cells-regulates-their-differentiation-within-lung-allografts-and-is-critical-for-tolerance-induction
#4
T Takahashi, H M Hsiao, S Tanaka, W Li, R Higashikubo, D Scozzi, A Bharat, J H Ritter, A S Krupnick, A E Gelman, D Kreisel
Immunological requirements for rejection and tolerance induction differ between various organs. While memory CD8(+) T cells are considered a barrier to immunosuppression-mediated acceptance of most tissues and organs, tolerance induction after lung transplantation is critically dependent on central memory CD8(+) T lymphocytes. Here we demonstrate that costimulation blockade-mediated tolerance after lung transplantation is dependent on PD-1 expression on CD8(+) T cells. In the absence of PD-1 expression, CD8(+) T cells form prolonged interactions with graft-infiltrating CD11c(+) cells, their differentiation is skewed towards an effector memory phenotype and grafts are rejected acutely...
July 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28729289/class-ii-eplet-mismatch-modulates-tacrolimus-trough-levels-required-to-prevent-donor-specific-antibody-development
#5
Chris Wiebe, David N Rush, Thomas E Nevins, Patricia E Birk, Tom Blydt-Hansen, Ian W Gibson, Aviva Goldberg, Julie Ho, Martin Karpinski, Denise Pochinco, Atul Sharma, Leroy Storsley, Arthur J Matas, Peter W Nickerson
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch...
July 20, 2017: Journal of the American Society of Nephrology: JASN
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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