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https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#1
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
#2
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/28220931/the-role-of-extracorporeal-photopheresis-in-the-management-of-cutaneous-t-cell-lymphoma-graft-versus-host-disease-and-organ-transplant-rejection-a-consensus-statement-update-from-the-uk-photopheresis-society
#3
Arun Alfred, Peter C Taylor, Fiona Dignan, Khaled El-Ghariani, James Griffin, Andrew R Gennery, Denise Bonney, Emma Das-Gupta, Sarah Lawson, Ram K Malladi, Kenneth W Douglas, Tracey Maher, Julie Guest, Laura Hartlett, Andrew J Fisher, Fiona Child, Julia J Scarisbrick
Extracorporeal photopheresis (ECP) has been used for over 35 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic and acute graft-versus-host disease (GvHD) and solid organ transplant rejection. ECP for CTCL and GvHD is available at specialised centres across the UK. The lack of prospective randomised trials in ECP led to the development of UK Consensus Statements for patient selection, treatment schedules, monitoring protocols and patient assessment criteria for ECP...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#4
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#5
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n=184), myelodysplastic syndrome (n=69), acute lymphocytic leukemia (n=57), chronic myelogenous leukemia (CML, n=36), lymphoid neoplasms (n=38), adult T-cell leukemia/lymphoma (n=18), and multiple myeloma (n=12)...
February 17, 2017: Biology of Blood and Marrow 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
#6
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/28214979/improved-prognostic-stratification-power-of-cibmtr-risk-score-with-the-addition-of-absolute-lymphocyte-and-eosinophil-counts-at-the-onset-of-chronic-gvhd
#7
Joon Ho Moon, Nada Hamad, Sang Kyun Sohn, Jieun Uhm, Naheed Alam, Vikas Gupta, Jeffrey H Lipton, Hans A Messner, Matthew Seftel, John Kuruvilla, Dennis Dong Hwan Kim
The CIBMTR chronic graft-versus-host disease (cGVHD) risk score can be refined and improved for better prognostic stratification. Three hundred and seven consecutive patients diagnosed with cGVHD by the NIH consensus criteria were retrospectively reviewed and had the CIBMTR risk score applied and analyzed. The CIBMTR risk score was successfully validated in our cohort (n = 307). The 3-year overall survival (OS) rates in each risk group (RG) were 82.5 ± 11.3% (RG1), 79.4 ± 3.0% (RG2), 71.8 ± 6.3% (RG3), and 27...
February 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28212937/the-impact-of-alemtuzumab-scheduling-on-graft-versus-host-disease-following-unrelated-donor-fludarabine-and-melphalan-allografts
#8
Kile Green, Kim Pearce, Rob S Sellar, Laura Jardine, Phillip Lr Nicolson, Sandeep Nagra, Venetia Bigley, Graham Jackson, Anne M Dickinson, Kirsty Thomson, Stephen Mackinnon, Charles Craddock, Karl S Peggs, Matthew Collin
Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft versus host disease (GVHD) in reduced intensity fludarabine and melphalan transplantation with ciclosporin monotherapy. Less frequent and lower dose scheduling may be used with sibling donors but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving three different dose schedules: the standard 100mg regimen (20mg on day -7 to -3), 60mg (30mg day -4 and -2) or 50mg (10mg on day -7 to -3)...
February 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28210258/human-gingiva-derived-mesenchymal-stem-cells-inhibit-xeno-graft-versus-host-disease-via-cd39-cd73-adenosine-and-ido-signals
#9
Feng Huang, Maogen Chen, Weiqian Chen, Jian Gu, Jia Yuan, Yaoqiu Xue, Junlong Dang, Wenru Su, Julie Wang, Homayoun H Zadeh, Xiaoshun He, Limin Rong, Nancy Olsen, Song Guo Zheng
Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209904/noninvasive-imaging-of-human-immune-responses-in-a-human-xenograft-model-of-graft-versus-host-disease
#10
Catharina H M J Van Elssen, Mohammad Rashidian, Vladimir Vrbanac, Kai W Wucherpfennig, Zeina El Habre, Jana Sticht, Christian Freund, Johanne Jacobsen, Juanjo Cragnolini, Jessica Ingram, Loes Plaisier, Eric Spierings, Andrew M Tager, Hidde Ploegh
The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer or auto-immunity. Immuno-PET is a non-invasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209721/the-cumulative-burden-of-double-stranded-dna-virus-detection-after-allogeneic-hct-is-associated-with-increased-mortality
#11
Joshua A Hill, Bryan T Mayer, Hu Xie, Wendy M Leisenring, Meei-Li Huang, Terry Stevens-Ayers, Filippo Milano, Colleen Delaney, Mohamed L Sorror, Brenda M Sandmaier, Garrett Nichols, Danielle M Zerr, Keith R Jerome, Joshua T Schiffer, Michael Boeckh
Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007-2014. We used quantitative PCR to test for cytomegalovirus (CMV), BK polyomavirus (BKV), human herpesvirus 6B (HHV-6B), HHV-6A, adenovirus (AdV), and Epstein-Barr virus (EBV) between days 0-100 post-HCT...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28209630/inhibition-of-phosphodiesterase-4-pde4-reduces-dermal-fibrosis-by-interfering-with-the-release-of-interleukin-6-from-m2-macrophages
#12
Christiane Maier, Andreas Ramming, Christina Bergmann, Rita Weinkam, Nicolai Kittan, Georg Schett, Jörg H W Distler, Christian Beyer
OBJECTIVES: To investigate the disease-modifying effects of phosphodiesterase 4 (PDE4) inhibition in preclinical models of systemic sclerosis (SSc). METHODS: We studied the effects of PDE4 inhibition in a prevention and a treatment model of bleomycin-induced skin fibrosis, in the topoisomerase mouse model as well as in a model of sclerodermatous chronic graft-versus-host disease. To better understand the mode of action of PDE4 blockade in preclinical models of SSc, we investigated fibrosis-relevant mediators in fibroblasts and macrophages from healthy individuals and patients suffering from diffuse-cutaneous SSc on blockade of PDE4...
February 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28207973/risk-factors-of-human-herpesvirus-6-encephalitis-myelitis-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
Naohiro Miyashita, Tomoyuki Endo, Masahiro Onozawa, Daigo Hashimoto, Takeshi Kondo, Katsuya Fujimoto, Kaoru Kahata, Junichi Sugita, Hideki Goto, Toshihiro Matsukawa, Satoshi Hashino, Takanori Teshima
BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis/myelitis is now a well-known complication after allogeneic stem cell transplantation (allo-HSCT), particularly after cord blood transplantation (CBT). In this study, we evaluated the risk factors of HHV-6 encephalitis/myelitis. METHODS: We evaluated 253 patients who received allo-HSCT from 2007 to 2015 at our institute. HHV-6 encephalitis/myelitis was defined as HHV-6 DNA detection in the cerebrospinal fluid or peripheral blood by polymerase chain reaction in the presence of typical manifestations without other concurrent condition which led to the manifestations...
February 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28206973/clinical-implications-of-hla-locus-mismatching-in-unrelated-donor-hematopoietic-cell-transplantation-a-meta-analysis
#14
REVIEW
Ruxiu Tie, Tiansong Zhang, Bo Yang, Huarui Fu, Biqing Han, Jian Yu, Yamin Tan, He Huang
It remains controversial that the impacts of individual HLA locus mismatches on clinical outcomes of patients receiving unrelated-donor hematopoietic cell transplantation (HCT), as compared to HLA allele matched controls. We conducted a meta-analysis to address these issues. Four databases (PubMed, Embase, Web of Science and the Cochrane Library) were searched to select eligible studies. All donor-recipient pairs were high-resolution typing for HLA-A, -B, -C, -DRB1, DQB1 and DPB1 loci. Multivariate-adjusted hazard ratios (HRs) were extracted and pooled using a random-effects model...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205066/a-single-center-analysis-of-chronic-graft-versus-host-disease-free-relapse-free-survival-after-alternative-donor-stem-cell-transplantation-in-children-with-hematological-malignancies
#15
Jiro Inagaki, Reiji Fukano, Maiko Noguchi, Jun Okamura
We assessed the clinical outcomes of allogeneic hematopoietic stem cell transplantation (SCT) from alternative donors for pediatric patients with hematological malignancies, defining graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) as a composite endpoint. We also defined chronic GVHD-free, relapse-free survival (cGRFS) as survival without severe chronic GVHD, relapse, or death. The probabilities of 2-year disease-free survival from a human leukocyte antigen (HLA) matched unrelated donor (n = 57), related donor with HLA-1 antigen mismatch in the graft-versus-host direction (1Ag-GvH-MMRD, n = 28), and unrelated umbilical cord blood (n = 35) were 52...
February 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28203622/a-case-of-eczema-coxsackium-with-erythema-multiforme-like-histopathology-in-a-14-year-old-boy-with-chronic-graft-versus-host-disease
#16
Patricia K Miller, Muhammad Zain-Ul-Abideen, Joan Paul, Ann E Perry, Konstantinos Linos, Joi B Carter, Joanne Kurtzberg, Julianne A Mann
No abstract text is available yet for this article.
January 2017: JAAD Case Reports
https://www.readbyqxmd.com/read/28199755/incidence-and-risk-factor-of-hemorrhagic-cystitis-after-allogeneic-transplantation-with-fludarabine-busulfan-and-anti-thymocyte-globulin-myeloablative-conditioning
#17
Wilson Lam, Jan Storek, Haocheng Li, Michelle Geddes, Andrew Daly
BACKGROUND: Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown. METHODS: We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality, GVHD, and healthcare resource use...
February 15, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28198960/quality-of-life-of-patients-with-graft-versus-host-disease-gvhd-post-hematopoietic-stem-cell-transplantation
#18
Sibéli de Fátima Ferraz Simão Proença, Celina Mattos Machado, Raquel de Castro Figueiredo Pereira Coelho, Leila Maria Mansano Sarquis, Paulo Ricardo Bittencourt Guimarães, Luciana Puchalski Kalinke
OBJECTIVE: Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD) is predictive of worse results. METHOD: An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT: The mean age was 37 years, 52...
November 2016: Revista da Escola de Enfermagem da U S P
https://www.readbyqxmd.com/read/28198910/alemtuzumab-as-graft-versus-host-disease-gvhd-prophylaxis-strategy-in-a-developing-country-lower-rate-of-acute-gvhd-increased-risk-of-cytomegalovirus-reactivation
#19
C B Resende, B M Rezende, P T T Bernardes, G M Teixeira, M M Teixeira, V Pinho, H Bittencourt
Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included...
February 9, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28198767/anti-gal-and-anti-neu5gc-responses-in-nonimmunosuppressed-patients-following-treatment-with-rabbit-anti-thymocyte-polyclonal-iggs
#20
Apolline Salama, Gwénaëlle Evanno, Noha Lim, Juliette Rousse, Ludmilla Le Berre, Arnaud Nicot, Sophie Brouard, Kristina M Harris, Mario R Ehlers, Stephen E Gitelman, Jean-Paul Soulillou
BACKGROUND: Polyclonal anti-human thymocyte rabbit IgGs (anti-thymocyte globulin, ATG) are popular immunosuppressive drugs used to prevent or treat organ or bone-marrow allograft rejection, graft versus host disease, and autoimmune diseases. However, animal-derived glycoproteins are also strongly immunogenic and rabbit ATG induces serum sickness disease in almost all patients without additional immunosuppressive drugs, as seen in the START trial of ATG therapy in new-onset type 1 diabetes...
February 14, 2017: Transplantation
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