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https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#1
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#2
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naïve and central memory T-cell populations, and activation of resting T-cells resulted in its decreased expression...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550042/t-cell-expression-of-ahr-inhibits-the-maintenance-of-ptreg-cells-in-the-gi-tract-in-acute-gvhd
#3
Trisha A Dant, Kaifeng L Lin, Danny W Bruce, Stephanie A Montgomery, Oleg V Kolupaev, Hemamalini Bommiasamy, Lisa M Bixby, John T Woosley, Karen P McKinnon, Frank J Gonzalez, Bruce R Blazar, Benjamin G Vincent, James M Coghill, Jonathan S Serody
The Aryl-hydrocarbon-receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR(-/-) T cells have improved survival and decreased acute graft versus host disease (aGvHD) in two different murine allogeneic bone marrow transplant models (BMT). We also show that CD4(+) T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue due to low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T cells (pTregs) in the colon of recipients transplanted with AhR(-/-) T cells 14 days after transplant...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549771/calcineurin-and-mtor-inhibitor-free-post-transplantation-cyclophosphamide-and-bortezomib-combination-for-graft-versus-host-disease-prevention-after-peripheral-blood-allogeneic-hematopoietic-stem-cell-transplantation-a-phase-i-ii-study
#4
A Samer Al-Homsi, Kelli Cole, Marlee Muilenburg, Austin Goodyke, Muneer Abidi, Ulrich Duffner, Stephanie Williams, Jessica Parker, Aly Abdel-Mageed
Graft-versus-host disease (GvHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GvHD. Patients undergoing peripheral blood AHSCT for hematological malignancies following reduced-intensity conditioning with grafts from human leukocyte antigen (HLA)-matched related or unrelated donors were enrolled in a phase I-II clinical trial...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#5
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28547857/confocal-endomicroscopy-in-diagnosis-of-intestinal-chronic-graft-versus-host-disease
#6
Kathrin Rieger, Ute Günther, Ulrike Erben, Anja Kühl, Christoph Loddenkemper, Antonio Pezzutto, Britta Siegmund, Christian Bojarski
Graft-versus-host disease (GvHD) is a major complication of allogeneic stem cell transplantation. High-resolution in vivo histology of the intestine by confocal endomicroscopy (CEM) detects acute GvHD (aGvHD) with high sensitivity. This pilot study aims to evaluate the diagnostic value of CEM for intestinal chronic GvHD (cGvHD). The study included 20 patients with gastrointestinal symptoms and confirmed cGvHD in other organs as well as 20 patients with clinically suspected acute GvHD for control. Confocal endomicroscopy was performed as gastroscopy followed by sigmoidoscopy after intravenous injection of fluorescein (10%) and topical application of acriflavine (0...
May 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28536366/advances-in-the-use-of-regulatory-t-cells-for-the-prevention-and-therapy-of-graft-vs-host-disease
#7
REVIEW
Reshma Ramlal, Gerhard C Hildebrandt
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product...
May 16, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#8
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536321/-disruption-of-gut-immune-system-caused-by-damage-of-intestinal-stem-cells-and-their-niche-in-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#9
Eiko Hayase, Takanori Teshima
Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. In intestinal GVHD, intestinal stem cells and Paneth cells reside at the base of crypts are damaged by donor T cells. These damage leads to disruption of intestinal mucosal barrier and intestinal dysbiosis, resulting in more exaggerated GVHD. Recently, we and others have reported that R-Spondin1 and interleukin-22 as factors regenerated intestinal tissue homeostasis in murine model of bone marrow transplantation...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28533059/graft-versus-host-disease-of-the-gut-a-histologic-activity-grading-system-and-validation
#10
David Myerson, Gideon Steinbach, Ted A Gooley, Howard M Shulman
The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We have developed a histologic activity grading system designed to replace the commonly used modified-Lerner grading systems...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28529723/role-of-major-histocompatibility-complex-variation-in-graft-versus-host-disease-after-hematopoietic-cell-transplantation
#11
REVIEW
Effie W Petersdorf
Graft-versus-host disease (GVHD) remains a significant potentially life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). Since the discovery of the human leukocyte antigen (HLA) system over 50 years ago, significant advances have clarified the nature of HLA variation between transplant recipients and donors as a chief etiology of GVHD. New information on coding and non-coding gene variation and GVHD risk provides clinicians with options to consider selected mismatched donors when matched donors are not available...
2017: F1000Research
https://www.readbyqxmd.com/read/28527984/personalized-prognostic-risk-score-for-long-term-survival-for-children-with-acute-leukemia-after-allogeneic-transplant
#12
Menachem Bitan, Kwang Woo Ahn, Heather R Millard, Michael A Pulsipher, Hisham Abdel-Azim, Jeffery J Auletta, Valerie Brown, Ka Wah Chan, Miguel Angel Diaz, Andrew Dietz, Marta González Vincent, Gregory Guilcher, Gregory A Hale, Robert J Hayashi, Amy Keating, Parinda Mehta, Kasiani Myers, Kristin Page, Tim Prestidge, Nirali N Shah, Angela R Smith, Ann Woolfrey, Elizabeth Thiel, Stella M Davies, Mary Eapen
We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML; n=790) and acute lymphoblastic leukemia (ALL; n=1096), transplanted between 2000 and 2010, who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease- and transplantation characteristics and acute and chronic graft versus host disease (GVHD) were performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival...
May 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28527401/prognostic-factors-on-graft-versus-host-disease-free-and-relapse-free-survival-after-allogeneic-hematopoietic-stem-cell-transplantation-for-adults-with-acute-leukemia
#13
Jie Tan, Ya Wang, Si-Jian Yu, Yong-Yong Ma, Hu-Yi Lei, Qi-Fa Liu
The cure of acute leukemia by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is closely linked to major complications leading to adverse outcomes, including graft-versus-host disease (GVHD), disease relapse and death. This study retrospectively investigated a consecutive series of 312 adult patients with acute leukemia receiving allo-HSCT by using a novel concept of GVHD-free/relapse-free survival (GRFS), and further evaluated the impact of clinical factors on GRFS. Results indicated that the 1- and 2-year GRFS were 54...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#14
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28524885/ocular-surface-analysis-in-hematological-patients-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-implication-for-daily-clinical-practice
#15
G Giannaccare, F Bonifazi, M Sessa, E Dan, M Arpinati, M Fresina, G Bandini, M Cavo, P Versura, E C Campos
PurposeTo evaluate ocular surface parameters before and after hematopoietic stem cell transplantation (HSCT) and to correlate them with clinical and transplant variables.MethodsThis is a retrospective analysis of data from 93 patients affected by hematological malignancies undergoing HSCT. Values from Ocular Surface Disease Index, Schirmer test, Break-up Time, ocular surface staining, and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Diagnosis and staging of dry eye (DE) disease was performed according to Dry Eye WorkShop criteria...
May 19, 2017: Eye
https://www.readbyqxmd.com/read/28524043/gvhd-like-erythroderma-in-the-clinical-course-of-thymoma-associated-myasthenia-gravis
#16
Hisashi Nomura, Shigeaki Suzuki, Fumiyo Yasuda-Sekiguchi, Masayuki Amagai, Satoshi Yamada, Jin Nakahara, Norihiro Suzuki, Mitsutomo Kohno, Takeru Funakoshi
No abstract text is available yet for this article.
May 19, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28522464/vitamin-a-to-reduce-gut-leak-and-gvhd
#17
Paul A Carpenter
No abstract text is available yet for this article.
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#18
M Hanief Sofi, Jessica Heinrichs, Mohammed Dany, Hung Nguyen, Min Dai, David Bastian, Steven Schutt, Yongxia Wu, Anusara Daenthanasanmak, Salih Gencer, Aleksandra Zivkovic, Zdzislaw Szulc, Holger Stark, Chen Liu, Ying-Jun Chang, Besim Ogretmen, Xue-Zhong Yu
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28506261/a-possible-role-of-low-regulatory-t-cells-in-anti-acetylcholine-receptor-antibody-positive-myasthenia-gravis-after-bone-marrow-transplantation
#19
Masahiko Fukatsu, Takenobu Murakami, Hiroshi Ohkawara, Shunichi Saito, Kazuhiko Ikeda, Suguru Kadowaki, Itaru Sasaki, Mari Segawa, Tomoko Soeda, Akihiko Hoshi, Hiroshi Takahashi, Akiko Shichishima-Nakamura, Kazuei Ogawa, Yoshihiro Sugiura, Hitoshi Ohto, Yasuchika Takeishi, Takayuki Ikezoe, Yoshikazu Ugawa
BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months...
May 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28504665/upper-gi-gvhd-similar-outcomes-to-other-grade-ii-graft-versus-host-disease
#20
R S Mehta, Q Cao, S Holtan, M L MacMillan, D J Weisdorf
The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD) compared with other grade II aGVHD is not clearly defined. We compared the outcomes of patients with grade II aGVHD with or without biopsy-proven UGI involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall response (ORR) to steroids at day 28 differed among the three groups (76, 67 and 91%, respectively, P=0.01), but was only marginally different in direct comparison with those without or with UGI aGVHD (P=0...
May 15, 2017: Bone Marrow Transplantation
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