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Transplant tolerance

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https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#1
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28226414/methylene-blue-for-the-treatment-of-intractable-pain-associated-with-oral-mucositis
#2
Carlos J Roldan, Kent Nouri, Thomas Chai, Billy Huh
Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develop intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative...
February 22, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#3
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222739/generation-of-donor-specific-tr1-cells-to-be-used-after-kidney-transplantation-and-definition-of-the-timing-of-their-in-vivo-infusion-in-the-presence-of-immunosuppression
#4
Bechara Mfarrej, Eleonora Tresoldi, Angela Stabilini, Alessia Paganelli, Rossana Caldara, Antonio Secchi, Manuela Battaglia
BACKGROUND: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. METHODS: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222086/equivalence-study-of-two-temperature-measurement-methods-in-febrile-adult-patients-with-cancer
#5
Tina M Mason, Abdelbaki Boubekri, Jennifer Lalau, Amy Patterson, Susan R Hartranft, Steven K Sutton
PURPOSE/OBJECTIVES: To assess equivalence of temperatures taken via temporal artery and oral methods in febrile inpatients with cancer.
. DESIGN: Repeated measures equivalence design.
. SETTING: 24-bed hematology-oncology unit and 36-bed blood and marrow transplantation unit at H. Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute-designated comprehensive cancer center in Tampa, Florida.
. SAMPLE: Convenience sample of 58 febrile inpatients using 60 temperature measurements...
March 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28222055/ex-situ-perfusion-of-human-limb-allografts-for-24-hours
#6
Nicole L Werner, Fares Alghanem, Stephanie L Rakestraw, Dylan C Sarver, Bruce Nicely, Richard E Pietroski, Paul Lange, Steven M Rudich, Christopher L Mendias, Alvaro Rojas-Pena, John C Magee, Robert H Bartlett, Kagan Ozer
BACKGROUND: Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. METHODS: Upper limbs were procured from brain-dead organ donors...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28219835/marked-in-vivo-donor-treg-expansion-via-il-2-and-tl1a-ig-stimulation-ameliorates-gvhd-but-preserves-gvl-in-recipients-post-hsct
#7
Dietlinde Wolf, Henry Barreras, Cameron S Bader, Sabrina Copsel, Casey O Lightbourn, Brent J Pfeiffer, Norman H Altman, Eckhard R Podack, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are critical for self-tolerance. While adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen and colon (a GVHD target tissue)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219694/lenalidomide-maintenance-in-patients-with-relapsed-diffuse-large-b-cell-lymphoma-who-are-not-eligible-for-autologous-stem-cell-transplantation-an-open-label-single-arm-multicentre-phase-2-trial
#8
Andrés J M Ferreri, Marianna Sassone, Francesco Zaja, Alessandro Re, Michele Spina, Alice Di Rocco, Alberto Fabbri, Caterina Stelitano, Maurizio Frezzato, Chiara Rusconi, Renato Zambello, Suzana Couto, Yan Ren, Annalisa Arcari, Giovanni Bertoldero, Alessandro Nonis, Lydia Scarfò, Teresa Calimeri, Caterina Cecchetti, Marianna Chiozzotto, Silvia Govi, Maurilio Ponzoni
BACKGROUND: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) not eligible for autologous stem cell transplantation (ASCT) or having relapse after ASCT have a low likelihood of cure. Single-drug maintenance after salvage therapy might be an attractive strategy to prolong survival in these patients. Lenalidomide is a suitable candidate for long-lasting maintenance as it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile. We designed a study to investigate safety and efficacy of lenalidomide maintenance in patients with chemosensitive relapse of DLBCL not eligible for ASCT or having relapse after ASCT...
February 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28218751/scleral-lenses-for-severe-chronic-gvhd-related-keratoconjunctivitis-sicca-a-retrospective-study-by-the-sfgm-tc
#9
L Magro, J Gauthier, M Richet, M Robin, S Nguyen, F Suarez, J-H Dalle, T Fagot, A Huynh, M-T Rubio, R Oumadely, S Vigouroux, N Milpied, A Delcampe, I Yakoub-Agha
Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28217256/interferon-free-regimens-in-patients-with-hepatitis-c-infection-and-renal-dysfunction-or-kidney-transplantation
#10
REVIEW
Evangelos Cholongitas, Chrysoula Pipili, George V Papatheodoridis
Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28214729/improved-tolerance-to-transplanting-injury-and-chilling-stress-in-rice-seedlings-treated-with-orysastrobin
#11
Naoto Takahashi, Yukari Sunohara, Masami Fujiwara, Hiroshi Matsumoto
In addition to their fungicidal activity, strobilurin-type fungicides are reported to show enhancing effects on crop growth and yield. Previous studies suggested that the fungicide has a mitigating effect on abiotic stresses. However, there are few reports about growth enhancement through abiotic stress alleviation by strobilurin-type fungicides, but the mechanism of action of the growth enhancement is still not clear. The present study revealed that orysastrobin enhanced rice seedling growth after root cutting injury and chilling stress...
February 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#12
REVIEW
Daniel J Firl, Gilles Benichou, James I Kim, Heidi Yeh
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#13
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207630/clinical-trials-for-immunosuppression-in-transplantation-the-case-for-reform-and-change-in-direction
#14
Philip J O'Connell, Dirk Kuypers, Roslyn R Mannon, Michael Abecassis, Stephen Chadban, John S Gill, Barbara Murphy, Peter W Nickerson, Jesse D Schold, Peter Stock, Daniel Seron, Rita Alloway, Jonathan Bromberg, Klemens Budde, Stanley Jordan, Christophe Legendre, Carmen Lefaucheur, Minnie Sarwall, Dorry Segev, Mark D Stegall, Stefan G Tullius, Germaine Wong, E Steve Woodle, Nancy Ascher, Randall E Morris
Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared to current standard of care. Current trial design is not leading to novel therapies improving long term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#15
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#16
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#17
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4(+) and CD8(+) Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4(+) and CD8(+) Foxp3(+) Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193829/soluble-cd83-inhibits-t-cell-activation-by-binding-to-the-tlr4-md-2-complex-on-cd14-monocytes
#18
Joe M Horvatinovich, Elizabeth W Grogan, Marcus Norris, Alexander Steinkasserer, Henrique Lemos, Andrew L Mellor, Irina Y Tcherepanova, Charles A Nicolette, Mark A DeBenedette
The transmembrane protein CD83, expressed on APCs, B cells, and T cells, can be expressed as a soluble form generated by alternative splice variants and/or by shedding. Soluble CD83 (sCD83) was shown to be involved in negatively regulating the immune response. sCD83 inhibits T cell proliferation in vitro, supports allograft survival in vivo, prevents corneal transplant rejection, and attenuates the progression and severity of autoimmune diseases and experimental colitis. Although sCD83 binds to human PBMCs, the specific molecules that bind sCD83 have not been identified...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#19
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188592/redirecting-reproductive-immunology-research-toward-pregnancy-as-a-period-of-temporary-immune-tolerance
#20
Norbert Gleicher, Vitaly A Kushnir, David H Barad
Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections...
February 10, 2017: Journal of Assisted Reproduction and Genetics
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