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https://www.readbyqxmd.com/read/29602451/-autologous-serum-tears-long-term-treatment-in-dry-eye-syndrome
#1
M Beylerian, M Lazaro, J Magalon, J Veran, A Darque, F Grimaud, N Stolowy, H Beylerian, F Sabatier, L Hoffart
INTRODUCTION: Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid...
March 27, 2018: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/29556230/ultra-sensitive-hiv-1-latency-viral-outgrowth-assays-using-humanized-mice
#2
REVIEW
Kimberly Schmitt, Ramesh Akkina
In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral outgrowth assays (qVOA) have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been inadequate in detecting the presence of ultralow levels of latent virus in a number of patients who were initially thought to have been cured, but eventually showed viral rebound. In this context, new approaches utilizing in vivo mouse-based VOAs are promising...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29549412/donor-recipient-killer-immunoglobulin-like-receptor-kir-genotype-matching-has-a-protective-effect-on-chronic-graft-versus-host-disease-and-relapse-incidence-following-hla-identical-sibling-hematopoietic-stem-cell-transplantation
#3
Ugur Sahin, Klara Dalva, Funda Gungor, Celalettin Ustun, Meral Beksac
Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene matching on transplant outcomes is still inconclusive. Recent data suggest that killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK cell) activity may contribute to graft versus leukemia (GvL) effects and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case-control study aims to evaluate the effects of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell replete HLA-identical sibling allo-HSCTs in a homogenous young patient population with myeloid leukemias...
March 16, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29500069/generation-of-alloreactivity-reduced-donor-lymphocyte-products-retaining-memory-function-by-fully-automatic-depletion-of-cd45ra-positive-cells
#4
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
February 28, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29386198/effect-of-non-permissive-hla-dpb1-mismatches-after-unrelated-allogeneic-transplantation-with-in-vivo-t-cell-depletion
#5
Betül Oran, Rima M Saliba, Yudith Carmazzi, Marcos de Lima, Gabriela Rondon, Sairah Ahmed, Amin Alousi, Borje S Andersson, Paolo Anderlini, Michelle Alvarez, Qasier Bashir, Stefan Ciurea, Marcelo Fernandez-Vina, Chitra Hosing, Partow Kebriaei, Martin Korbling, Pedro Cano, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Uday Popat, Katy Rezvani, Muzaffar Qazilbash, Elizabeth J Shpall, Richard E Champlin, Kai Cao
We investigated the impact of donor-recipient HLA-DPB1 matching on outcomes of allogeneic hematopoietic stem cell transplantation with in vivo T cell depletion using ATG for patients with hematological malignancies. All donor-recipient pairs had high resolution typing for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 and -DRB3/4/5 and were matched at HLA-A, -B, -C and -DRB1. HLA-DPB1 mismatches were categorized by immunogenicity of the DPB1 matching using the DPB T-cell epitope tool. Of 1004 donor-recipient pairs, 210 (21%) were DPB1 matched, 443 (44%) had permissive mismatches, 184 (18%) non-permissive mismatches, in graft versus host (GvH) direction and 167 (17%) non-permissive mismatches in host versus graft (HvG) direction...
January 31, 2018: Blood
https://www.readbyqxmd.com/read/29361165/single-blood-transfusion-induces-the-production-of-donor-specific-alloantibodies-and-regulatory-t-cells-mainly-in-the-spleen
#6
Hisashi Ueta, Yusuke Kitazawa, Yasushi Sawanobori, Takamasa Ueno, Satoshi Ueha, Kouji Matsushima, Kenjiro Matsuno
Donor-specific blood transfusion is known to induce alloresponses and lead to immunosuppression. We examined their underlying mechanisms by employing fully allogeneic rat combinations. Transfused recipients efficiently produced alloantibodies of the IgM and IgG subclasses directed against donor class I MHC. The recipients exhibited active expansion of CD4+ T-cells and CD4+FOXP3+ Treg cells, followed by CD45R+ B-cells and IgM+ or IgG subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the resident MHCII+CD103+ dendritic cells in the splenic T-cell area, periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl-2'-deoxyuridine+ cells, from which the proliferative response of CD4+ T-cells originated peaking at 3-4 days...
January 18, 2018: International Immunology
https://www.readbyqxmd.com/read/29355721/selecting-the-best-donor-for-haploidentical-transplant-impact-of-hla-kir-genotyping-and-other-clinical-variables
#7
Scott R Solomon, Michael A Aubrey, Xu Zhang, Allison Piluso, Brian M Freed, Stacey Brown, Katelin C Jackson, Lawrence E Morris, H Kent Holland, Melhem M Solh, Asad Bashey
The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, as multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age was 52 (19-75) and 38 (15-73) years, PBSC was the stem cell source in 66%, and myeloablative conditioning was used in 41%...
January 17, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29285209/combination-of-il-2-rapamycin-dna-methyltransferase-and-histone-deacetylase-inhibitors-for-the-expansion-of-human-regulatory-t-cells
#8
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+ T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FoxP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274116/risk-of-hla-homozygous-cord-blood-transplantation-implications-for-induced-pluripotent-stem-cell-banking-and-transplantation
#9
Yasuo Morishima, Fumihiro Azuma, Koichi Kashiwase, Kayoko Matsumoto, Takeshi Orihara, Hiromasa Yabe, Shunichi Kato, Koji Kato, Shunro Kai, Tetsuo Mori, Kazunori Nakajima, Satoko Morishima, Masahiro Satake, Minoko Takanashi, Toshio Yabe
Clinical application of induced pluripotent stem cells (iPS) in autologous settings has just begun. To overcome the high time and cost barriers in the individual production of autologous iPS, the use of allogeneic iPS with a homozygous human leukocyte antigen (HLA) haplotype (HLA-homo HP) has been proposed. Cord blood transplantation (CBT) is a suitable model for evaluating the allogeneic immunogenicity of iPS transplantation from HLA-homo donors. We analyzed 1,374 Japanese single cord blood transplant pairs who were retrospectively typed as HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1...
February 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29177692/dermatological-complications-after-solid-organ-transplantation
#10
REVIEW
Luigi Naldi, Anna Venturuzzo, Pietro Invernizzi
Organ transplant recipients (OTRs) are a population at high risk for cutaneous adverse events. Their early recognition and appropriate treatment is an important component of the clinical management of OTRs and should be optimally dealt with by dermatologists working in the context of a transplant dermatology clinic. Skin examination should be a standard procedure before performing organ transplantation to assess conditions which may be difficult to manage after the transplant procedure has been performed or which may represent a contraindication to transplantation, e...
February 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29024804/impact-of-hla-disparity-in-haploidentical-bone-marrow-transplantation-followed-by-high-dose-cyclophosphamide
#11
Anna Maria Raiola, Antonio Risitano, Nicoletta Sacchi, Livia Giannoni, Alessio Signori, Sara Aquino, Stefania Bregante, Carmen Di Grazia, Alida Dominietto, Simona Geroldi, Anna Ghiso, Francesca Gualandi, Teresa Lamparelli, Elisabetta Tedone, Maria Teresa Van Lint, Riccardo Varaldo, Adalberto Ibatici, Carlo Marani, Serena Marotta, Fabio Guolo, Daniele Avenoso, Lucia Garbarino, Fabrizio Pane, Andrea Bacigalupo, Emanuele Angelucci
We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction...
January 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28853768/systemic-treatment-with-a-mir-146a-mimic-suppresses-endotoxin-sensitivity-and-partially-protects-mice-from-the-progression-of-acute-graft-versus-host-disease
#12
J G Gartner, M M Durston, S A Booth, C A Ellison
Acute GVHD (aGVHD) is driven by interactions between the allogenic T cell response, inflammation, tissue injury and microbial products that enter the circulation when protective barriers such as the intestinal epithelium become compromised. Mice with aGVHD become hypersensitive to LPS, secreting large quantities of inflammatory mediators that exacerbate tissue injury. We hypothesized that microRNA (miR) modulators could be used in vivo to mitigate LPS hypersensitivity, altering the course of aGVHD. Using the C57BL/6 → (C57BL/6 × DBA/2)F1 -hybrid model of aGVHD, we measured intestinal permeability over time and used a qPCR array to detect concomitant changes in the expression levels of certain microRNAs (miRs) in the intestine...
November 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28826941/mechanisms-of-mixed-chimerism-based-transplant-tolerance
#13
REVIEW
Julien Zuber, Megan Sykes
Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells...
November 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28648733/-is-transplantation-an-alternative-to-the-transfusional-impasse-in-sickle-cell-disease
#14
F Bernaudin, M Kuentz
Sickle cell disease is the most frequent genetic disease in France, concerning 400 newborns each year. The management of these Afro-Caribbean patients requires frequent transfusions from Caucasian donors. Due to important erythroid antigenic differences between Caucasian and African, the prevalence of allo-immunization is high in this population with a risk of transfusional impasse. Allogeneic stem cell transplantation is the only curative treatment for this disease and the replacement of red cells and lymphocytes of the sickle cell patient by those of the donor can also resolve the transfusional impasse...
June 22, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28581467/directionality-of-non-permissive-hla-dpb1-t-cell-epitope-group-mismatches-does-not-improve-clinical-risk-stratification-in-8-8-matched-unrelated-donor-hematopoietic-cell-transplantation
#15
K Fleischhauer, K W Ahn, H L Wang, L Zito, P Crivello, C Müller, M Verneris, B E Shaw, J Pidala, M Oudshorn, S J Lee, S R Spellman
In 8/8 HLA-matched unrelated donor (UD) hematopoietic cell transplants (HCT), HLA-DPB1 mismatches between alleles from different T-cell epitope (TCE) groups (non-permissive mismatches) are associated with significantly higher risks of mortality compared with those between alleles from the same TCE group (permissive mismatches); however, the relevance of mismatch directionality, that is (host vs graft (uni-directional HvG), graft vs host (uni-directional GvH) or both (bi-directional) in the non-permissive setting is unknown...
September 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#16
Balasai Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4+ T cells in peripheral blood and lymph nodes...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28399164/sequential-monitoring-of-lymphocyte-subsets-and-of-t-and-b-cell-neogenesis-indexes-to-identify-time-varying-immunologic-profiles-in-relation-to-graft-versus-host-disease-and-relapse-after-allogeneic-stem-cell-transplantation
#17
Cristina Skert, Simone Perucca, Marco Chiarini, Viviana Giustini, Alessandra Sottini, Claudia Ghidini, Stefano Martellos, Federica Cattina, Benedetta Rambaldi, Valeria Cancelli, Michele Malagola, Alessandro Turra, Nicola Polverelli, Simona Bernardi, Luisa Imberti, Domenico Russo
T and B lymphocyte subsets have been not univocally associated to Graft-versus-host disease (GVHD) and relapse of hematological malignancies after stem cell transplantation (SCT). Their sequential assessment together with B and T cell neogenesis indexes has been not thoroughly analysed in relation to these changing and interrelated immunologic/clinic events yet. Lymphocyte subsets in peripheral blood (PB) and B and T cell neogenesis indexes were analysed together at different time points in a prospective study of 50 patients...
2017: PloS One
https://www.readbyqxmd.com/read/28239678/bidirectional-intragraft-alloreactivity-drives-the-repopulation-of-human-intestinal-allografts-and-correlates-with-clinical-outcome
#18
Julien Zuber, Brittany Shonts, Sai-Ping Lau, Aleksandar Obradovic, Jianing Fu, Suxiao Yang, Marion Lambert, Shana Coley, Joshua Weiner, Joseph Thome, Susan DeWolf, Donna L Farber, Yufeng Shen, Sophie Caillat-Zucman, Govind Bhagat, Adam Griesemer, Mercedes Martinez, Tomoaki Kato, Megan Sykes
A paradigm in transplantation states that graft-infiltrating T cells are largely non-alloreactive "bystander" cells. However, the origin and specificity of allograft T cells over time has not been investigated in detail in animals or humans. Here, we use polychromatic flow cytometry and high throughput TCR sequencing of serial biopsies to show that gut-resident T cell turnover kinetics in human intestinal allografts are correlated with the balance between intra-graft host-vs-graft (HvG) and graft-vs-host (GvH) reactivities and with clinical outcomes...
October 2016: Science Immunology
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
#19
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...
May 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27919187/diagnostic-value-of-serum-ferritin-and-the-risk-factors-and-cytokine-profiles-of-hemophagocytic-syndrome-following-allogeneic-hematopoietic-cell-transplantation
#20
Satoru Nanno, Hideo Koh, Yasuhiro Nakashima, Takako Katayama, Hiroshi Okamura, Shiro Koh, Takuro Yoshimura, Mitsutaka Nishimoto, Yoshiki Hayashi, Mika Nakamae, Asao Hirose, Takahiko Nakane, Masayuki Hino, Hirohisa Nakamae
To examine the diagnostic value of serum ferritin, the associated risk factors, and cytokine profiles of hemophagocytic syndrome (HPS) following allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively analyzed data from patients undergoing allo-HCT between 2006 and 2012. Of 223 eligible patients, 18 patients developed HPS. A serum ferritin level above 30,000 μg/l was highly specific for the detection of HPS (specificity, 93%). The one-year survival rate for HPS was significantly lower than that of non-HPS patients (37...
July 2017: Leukemia & Lymphoma
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