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https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#1
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423227/a-national-survey-of-screening-and-management-of-hypogammaglobulinemia-in-canadian-transplantation-centers
#2
Samuel Bourassa-Blanchette, Greg Knoll, Jason Tay, Christopher Bredeson, Donald W Cameron, Juthaporn Cowan
BACKGROUND: Infection remains one of the most common transplant-related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and clinical equipoise accounts for non-uniform practice in the use of Ig treatment...
April 18, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28412518/recipient-immune-modulation-with-atorvastatin-for-acute-graft-versus-host-disease-prophylaxis-following-allogeneic-transplantation
#3
Abraham S Kanate, Parameswaran N Hari, Marcelo C Pasquini, Alexis Visotcky, Kwang W Ahn, Jennifer Boyd, Guru Subramanian Guru Murthy, J Douglas Rizzo, Wael Saber, William Drobyski, Laura Michaelis, Ehab Atallah, Karen S Carlson, Anita D'Souza, Timothy S Fenske, Aaron Cumpston, Pamela Bunner, Michael Craig, Mary M Horowitz, Mehdi Hamadani
Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n=30) or matched unrelated donor (MUD; n=39) allo-HCT, enrolled in two separate cohorts...
April 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28404894/induction-and-characterization-of-anti-tumor-endothelium-immunity-elicited-by-vallovax-therapeutic-cancer-vaccine
#4
Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari
ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28344058/possible-impact-of-cmv-specific-cd8-t-cells-on-immune-reconstitution-and-conversion-to-complete-donor-chimerism-after-allogeneic-sct
#5
Justyna Ogonek, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Sylvia Borchers, Ulrike Koehl, Eva M Weissinger, Lothar Hambach
Complete donor chimerism is strongly associated with complete remission after allogeneic stem cell transplantation (allo-SCT) in patients with hematological malignancies. Donor-derived allo-immune responses are eliminating the residual host hematopoiesis and thereby mediate the conversion to complete donor chimerism. Recently, CMV reactivation has been described to enhance overall T-cell reconstitution, to increase graft-versus-host disease (GvHD) incidence and to reduce the leukemia relapse risk. However, the link between CMV and allo-immune responses is still unclear...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28343935/blood-derived-products-in-pediatrics-new-laboratory-tools-for-optimizing-potency-assignment-and-reducing-side-effects
#6
REVIEW
Jean Amiral, Jerard Seghatchian
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks...
March 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28340805/association-between-hla-antibodies-and-different-sensitization-events-in-renal-transplant-candidates
#7
S U Akgul, H S Ciftci, S Temurhan, Y Caliskan, A Bayraktar, T Tefik, I A Kaya, I O Canitez, E Demir, H Yazici, H Bakkaloglu, A E Aydin, A Turkmen, I Nane, F Aydin, F S Oguz
BACKGROUND: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex)...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28298913/cathepsin-e-deficiency-ameliorates-graft-versus-host-disease-and-modifies-dendritic-cell-motility
#8
Jörg Mengwasser, Liane Babes, Steffen Cordes, Sarah Mertlitz, Katarina Riesner, Yu Shi, Aleixandria McGearey, Martina Kalupa, Thomas Reinheckel, Olaf Penack
Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28296584/intestinal-microbiota-and-relapse-after-hematopoietic-cell-transplantation
#9
Jonathan U Peled, Sean M Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B Slingerland, Katya F Ahr, Kori A Porosnicu Rodriguez, Yusuke Shono, Ann E Slingerland, Melissa D Docampo, Anthony D Sung, Daniela Weber, Amin M Alousi, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Ying Taur, Eric G Pamer, Robert R Jenq, Marcel R M van den Brink
Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT...
March 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28292332/aberrant-t-cell-responses-in-the-bone-marrow-microenvironment-of-patients-with-poor-graft-function-after-allogeneic-hematopoietic-stem-cell-transplantation
#10
Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD)...
March 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28286199/abnormalities-of-the-bone-marrow-immune-microenvironment-in-patients-with-prolonged-isolated-thrombocytopenia-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
Yang Song, Min-Min Shi, Yuan-Yuan Zhang, Xiao-Dong Mo, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang, Yuan Kong
Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) immune microenvironment are involved in the pathogenesis of PT remains unknown, however. Twenty patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD) were enrolled in this nested case-control study. Th1, Th2, Tc1, Tc2, Th17, and Treg cells were analyzed by flow cytometry, and IFN-γ, IL-4, IL-17, IL-6, IL-21, and thrombopoietin levels in BM plasma were evaluated with a cytometric bead assay and ELISA...
March 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28285435/allogeneic-hematopoietic-cell-transplantation-for-myeloma-when-and-in-whom-does-it-work
#12
REVIEW
Qaiser Bashir, Muzaffar H Qazilbash
The growing list of available therapies for patients with multiple myeloma has resulted in tremendously high response rates and prolonged survival. However, the cure remains elusive. A continued effort at developing strategies to utilize all available treatment modalities in the most effective manner is needed. Allogeneic hematopoietic cell transplantation (allo-HCT) is a robust platform, associated with high response rates, and provides a unique foundation on which immune therapies and novel agents can be employed to improve clinical outcomes...
March 11, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28281429/single-centre-experience-of-allogeneic-haemopoietic-stem-cell-transplant-in-paediatric-patients-in-cape-town-south-africa
#13
A Van Eyssen, N Novitsky, P De Wit, T Schlaphoff, V Thomas, D Pillay, M Hendricks, A Davidson
BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS)...
February 27, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28255564/endothelial-cells-in-antibody-mediated-rejection-of-kidney-transplantation-pathogenesis-mechanisms-and-therapeutic-implications
#14
REVIEW
Shuo Wang, Chao Zhang, Jina Wang, Cheng Yang, Ming Xu, Ruiming Rong, Tongyu Zhu, Dong Zhu
Antibody-mediated rejection (AMR) has been identified as a main obstacle for stable immune tolerance and long survival of kidney allografts. In spite of new insights into the underlying mechanisms of AMR, accurate diagnosis and efficient treatment are still challenges in clinical practice. Endothelium is the first barrier between recipients' immune systems and grafts in vascularized organ transplants. Considering that endothelial cells express a number of antigens that can be attacked by various allo- and autoantibodies, endothelial cells act as main targets for the recipients' humoral immune responses...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28252558/mismatched-hla-drb3-can-induce-a-potent-immune-response-after-hla-10-10-matched-stem-cell-transplantation
#15
Peter van Balen, Simon A P van Luxemburg-Heijs, Marian van de Meent, Cornelis A M van Bergen, Constantijn J M Halkes, Inge Jedema, J H Frederik Falkenburg
BACKGROUND: Donors for allogeneic stem cell transplantation (alloSCT) are preferentially matched with patients for HLA-A, B, C and DRB1. Mismatches between donor and patient in these alleles are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with limited relevance, although mismatches in HLA-DQ and HLA-DP can result in allo-immune responses. Mismatches in HLA-DRB3, 4 and 5 are usually not taken into account in donor selection...
March 1, 2017: Transplantation
https://www.readbyqxmd.com/read/28224776/clinical-usefulness-of-monitoring-cytomegalovirus-specific-immunity-by-quantiferon-cmv-in-pediatric-allogeneic-hematopoietic-stem-cell-transplantation-recipients
#16
Sae Mi Lee, Yae Jean Kim, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Eun Suk Kang
Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT...
May 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28219579/glomerular-diseases-and-renal-transplantation-pathogenic-pathways-and-evolution-of-therapeutic-interventions
#17
S Marinaki, C Skalioti, J Boletis
Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28188669/orthogonal-comparison-of-molecular-signatures-of-kidney-transplants-with-subclinical-and-clinical-acute-rejection-equivalent-performance-is-agnostic-to-both-technology-and-platform
#18
S M Kurian, E Velazquez, R Thompson, T Whisenant, S Rose, N Riley, F Harrison, T Gelbart, J J Friedewald, J Charrette, S Brietigam, J Peysakhovich, M R First, M M Abecassis, D R Salomon
We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28170189/mesenchymal-stem-cells-yield-transient-improvements-in-motor-function-in-an-infant-rhesus-macaque-with-severe-early-onset-krabbe-disease
#19
Irina A Isakova, Kate C Baker, Jason Dufour, Donald G Phinney
Krabbe disease, or globoid cell leukodystrophy, is a rare disorder caused by deficient galactosylceramidase activity and loss of myelin-forming oligodendrocytes, resulting in progressive demyelination and severely impaired motor function. Disease symptoms in humans appear within 3-6 months of age (early infantile) and manifest as marked irritability, spasticity, and seizures. The disease is often fatal by the second year of life, with few effective treatment options. Herein we evaluated the therapeutic potential of mesenchymal stem cells (MSCs) administered intracranially to a 1-month-old rhesus macaque diagnosed with severe early-onset Krabbe disease that displayed neurologic and behavioral symptoms similar to those of human patients...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28148718/role-of-myeloid-derived-suppressor-cells-in-allogeneic-hematopoietic-cell-transplantation
#20
REVIEW
Brent H Koehn, Bruce R Blazar
Graft-versus-host disease (GVHD) can be a devastating complication for as many as a third of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). A role for myeloid cells in the amplification of GVHD has been demonstrated; however, less is understood about a potential regulatory role that myeloid cells play or whether such cells may be manipulated and applied therapeutically. Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population that are engaged and expand shortly after many forms of immune distress, including cancer, trauma, and infection...
February 1, 2017: Journal of Leukocyte Biology
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