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https://www.readbyqxmd.com/read/29348821/glycan-microarray-reveal-induced-iggs-repertoire-shift-against-a-dietary-carbohydrate-in-response-to-rabbit-anti-human-thymocyte-therapy
#1
Ron Amon, Shani Leviatan Ben-Arye, Limor Engler, Hai Yu, Noha Lim, Ludmilla Le Berre, Kristina M Harris, Mario R Ehlers, Stephen E Gitelman, Xi Chen, Jean-Paul Soulillou, Vered Padler-Karavani
Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29335632/long-term-outcome-analysis-of-reduced-intensity-allogeneic-stem-cell-transplantation-in-patients-with-mantle-cell-lymphoma-a-retrospective-study-from-the-ebmt-lymphoma-working-party
#2
Stephen P Robinson, Ariane Boumendil, Herve Finel, Karl S Peggs, Patrice Chevallier, Jorge Sierra, Jürgen Finke, Xavier Poiré, Natacha Maillard, Noël Milpied, Ibrahim Yakoub-Agha, Mickey Koh, Nicolaus Kröger, Arnon Nagler, Yener Koc, Sascha Dietrich, Silvia Montoto, Peter Dreger
Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330484/single-cell-rna-sequencing-resolves-self-antigen-expression-during-mtec-development
#3
Ricardo J Miragaia, Xiuwei Zhang, Tomás Gomes, Valentine Svensson, Tomislav Ilicic, Johan Henriksson, Gozde Kar, Tapio Lönnberg
The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330161/production-of-bmp4-by-endothelial-cells-is-crucial-for-endogenous-thymic-regeneration
#4
Tobias Wertheimer, Enrico Velardi, Jennifer Tsai, Kirsten Cooper, Shiyun Xiao, Christopher C Kloss, Katja J Ottmüller, Zeinab Mokhtari, Christian Brede, Paul deRoos, Sinéad Kinsella, Brisa Palikuqi, Michael Ginsberg, Lauren F Young, Fabiana Kreines, Sophia R Lieberman, Amina Lazrak, Peipei Guo, Florent Malard, Odette M Smith, Yusuke Shono, Robert R Jenq, Alan M Hanash, Daniel J Nolan, Jason M Butler, Andreas Beilhack, Nancy R Manley, Shahin Rafii, Jarrod A Dudakov, Marcel R M van den Brink
The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair...
January 12, 2018: Science Immunology
https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#5
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29325312/-outcomes-of-alternative-donor-allogeneic-hematopoietic-stem-cell-transplantation-for-fanconi-anemia-a-five-cases-report
#6
W J Wang, Y Q Sun, F F Tang, T T Han, X D Mo, J Z Wang, X H Zhang, X J Huang, L P Xu
Five patients with Fanconi anemia who received hematopoietic cell transplantation were retrospectively analyzed. The conditioning regimens included fludarabine, cyclophosphamide and anti-thymocyte globulin. Two patients received both bone marrow and peripheral blood stem cells as the source of stem cell grafts from haploidentical matched related donors, while the others received peripheral blood stem cells from unrelated donors. All patients tolerated well and reached hematopoietic reconstitution. One patient died of intracranial infection...
January 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29323266/aif-loss-deregulates-hematopoiesis-and-reveals-different-adaptive-metabolic-responses-in-bone-marrow-cells-and-thymocytes
#7
Lauriane Cabon, Audrey Bertaux, Marie-Noëlle Brunelle-Navas, Ivan Nemazanyy, Laurianne Scourzic, Laure Delavallée, Laura Vela, Mathieu Baritaud, Sandrine Bouchet, Cécile Lopez, Vu Quang Van, Kevin Garbin, Danielle Chateau, Françoise Gilard, Marika Sarfati, Thomas Mercher, Olivier A Bernard, Santos A Susin
Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was associated with hypocellular bone marrow (BM) and thymus atrophy. Although myeloid cells were relatively spared, the B-cell and erythroid lineages were altered with increased frequencies of precursor B cells, pro-erythroblasts I, and basophilic erythroblasts II...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29321275/cd40-mediates-maturation-of-thymic-dendritic-cells-driven-by-self-reactive-cd4-thymocytes-and-supports-development-of-natural-regulatory-t-cells
#8
Jaehak Oh, Nan Wu, Andrea J Barczak, Rebecca Barbeau, David J Erle, Jeoung-Sook Shin
Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4+ thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29319768/the-current-burden-of-cytomegalovirus-infection-in-kidney-transplant-recipients-receiving-no-pharmacological-prophylaxis
#9
Claudia Rosso Felipe, Alexandra Nicolau Ferreira, Adrieli Bessa, Tamiris Abait, Priscilla Ruppel, Mayara Ivani de Paula, Liliane Hiramoto, Laila Viana, Suelen Martins, Marina Cristelli, Wilson Aguiar, Juliana Mansur, Geovana Basso, Helio Tedesco Silva Junior, Jose Medina Pestana
Cytomegalovirus (CMV) infection in kidney transplantation has changed its clinical spectrum, mostly due to the current and more effective immunosuppression. In the absence of preventive strategies it is associated with significant morbi-mortality. OBJECTIVE: This study evaluated the incidence of CMV events and its effect on outcomes of kidney transplantation in recipients without pharmacological prophylaxis or targeted preemptive treatment. RESULTS: The study cohort comprised 802 recipients of kidney transplants between 04/30/2014 and 04/30/2015...
October 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29318612/transplanted-human-thymus-slices-induce-and-support-t-cell-development-in-mice-after-cryopreservation
#10
Susan Ross, Melissa Cheung, Ching-In Lau, Neil Sebire, Michael Burch, Peter Kilbride, Barry Fuller, G John Morris, E Graham Davies, Tessa Crompton
Here we show that slices of human thymus tissue that have been frozen and thawed can induce and support T-cell development when transplanted into nude mice. Babies born without a thymus require urgent treatment to reconstitute T-cell immunity. Thymus tissue is removed from infants during cardiac surgery, to allow access to the heart. This discarded thymus tissue can be transplanted into athymic infants to reconstitute T-cell immunity. Slices of thymus tissue are transplanted into the thigh, after a two-three week culture period to deplete thymocytes...
January 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancera
#11
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 9, 2018: Small GTPases
https://www.readbyqxmd.com/read/29306655/comparative-study-of-porcine-anti-human-lymphocyte-immunoglobulin-and-rabbit-anti-human-thymocyte-immunoglobulin-as-a-first-line-treatment-of-acquired-severe-aplastic-anemia
#12
Miao Chen, Chao Liu, Xinhui Qiao, Daobin Zhou, Junling Zhuang, Bing Han
Porcine anti-human lymphocyte immunoglobulin (pALG) and rabbit anti-human thymocyte immunoglobulin (rATG) are the only two ATGs for severe aplastic anemia (SAA) treatment in China. 148 treatment-naïve SAA patients who received ATG combined with cyclosporine A (CsA) therapy were analysed retrospectively. The patients were divided into a pALG group (n = 114) and a rATG group (n = 34). After three months, the pALG and rATG groups had an overall response (OR) of 65.8% and 44.1%, respectively (P = 0...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29305907/association-between-biomechanical-alterations-and-migratory-ability-of-semaphorin-3a-treated-thymocytes
#13
Marvin Paulo Lins, Elaine Cristina Oliveira da Silva, Givanildo Rodrigues da Silva, Samuel Teixeira de Souza, Navylla Candeia de Medeiros, Eduardo Jorge da Silva Fonseca, Salete Smaniotto
BACKGROUND: Class 3 semaphorins are soluble proteins involved in cell adhesion and migration. Semaphorin-3A (Sema3A) was initially shown to be involved in neuronal guidance, and it has also been reported to be associated with immune disorders. Both Sema3A and its receptors are expressed by most immune cells, including monocytes, macrophages, and lymphocytes, and these proteins regulate cell function. Here, we studied the correlation between Sema3A-induced changes in biophysical parameters of thymocytes, and the subsequent repercussions on cell function...
January 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29303047/eltrombopag-in-the-management-of-aplastic-anaemia-real-world-experience-in-a-non-trial-setting
#14
Yu-Yan Hwang, Harinder Gill, Thomas S Y Chan, Garret M K Leung, Carol Y M Cheung, Yok-Lam Kwong
OBJECTIVE: The thrombopoietin mimetic eltrombopag has been used in clinical trials for the frontline and salvage treatment of aplastic anaemia (AA). Eltrombopag was investigated in AA patients on a non-trial all-comer basis. METHODS: Consecutive newly diagnosed and relapsed/refractory AA patients were treated with eltrombopag. RESULTS: In a 4.5-year period, 20 consecutive AA patients (newly diagnosed, N = 10; relapsed/refractory, N = 10) at a median age of 47 (22-84) years were treated with eltrombopag...
January 5, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29298829/cellularity-of-thymic-epithelial-cells-in-the-postnatal-mouse
#15
Mie Sakata, Izumi Ohigashi, Yousuke Takahama
The molecular and cellular biology of thymic epithelial cells (TECs) often relies on the analysis of TECs isolated in enzymatically digested single-cell suspensions derived from mouse thymus. Many independent studies have reported that the estimated cellularity of total TECs isolated from one adult mouse is on the order of up to 105 However, these numbers appear extremely small given that the cellularity of total thymocytes exceeds 108 and that TECs play multiple roles in thymocyte development and repertoire formation...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29296761/alternative-donor-hematopoietic-stem-cell-transplantation-for-sickle-cell-disease
#16
Andrew L Gilman, Michael J Eckrich, Stacy Epstein, Carrie Barnhart, Mark Cannon, Tracy Fukes, Michelle Hyland, Krishna Shah, Darci Grochowski, Elizabeth Champion, Anastasia Ivanova
Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell-depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296723/atg-vs-thiotepa-with-busulfan-and-cyclophosphamide-in-matched-related-bone-marrow-transplantation-for-thalassemia
#17
Lawrence Faulkner, Cornelio Uderzo, Sadaf Khalid, Priya Marwah, Rajpreet Soni, Naila Yaqub, Samina Amanat, Itrat Fatima, Sarah Khan Gilani, Tatheer Zahra, Stalin Ramprakash, Lallindra Gooneratne, Ruwangi Dissanayake, Senani Williams, Wasantha Rathnayake, Reshma Srinivas, Amit Sedai, Ankita Kumari, Lailith Parmar, Rakesh Dhanya, Rajat Kumar Agarwal
Matched-related bone marrow transplantation (BMT) may cure >80% of low-risk children with severe thalassemia (ST). Very long-term follow-up studies have shown how the standard busulfan-cyclophosphamide (BuCy) regimen may be associated with normalization of health-related quality of life, no second malignancies in the absence of chronic graft-versus-host disease, and fertility preservation in many patients. However, because BuCy may be associated with high rejection rates, some centers incorporate thiotepa (Tt) in busulfan- or treosulfan-based regimens, a combination that may increase the risk of permanent infertility...
May 23, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290091/breastfeeding-regulates-development-of-immune-system-through-tgf-%C3%AE-in-mice-pups
#18
Keita Sakaguchi, Akemi Koyanagi, Fumitaka Kamachi, Akiko Harauma, Asako Chiba, Ken Hisata, Toru Moriguchi, Toshiaki Shimizu, Sachiko Miyake
BACKGROUND: Breast milk contains important nutrients and immunoregulatory factors that are essential for newborn infants. Recently, epidemiological studies suggested that breastfeeding prevents a wide range of infectious diseases and lowers the incidence of infant allergic diseases. METHODS: To examine the effects of breast milk in immunological development in infancy, we established an artificial rearing system for hand-feeding mice and compared mouse pups fed with either breast milk or milk substitute...
December 31, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#19
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29288207/newly-generated-cd4-t-cells-acquire-metabolic-quiescence-after-thymic-egress
#20
Shusong Zhang, Xinwei Zhang, Ke Wang, Xi Xu, Mingyang Li, Jun Zhang, Yan Zhang, Jie Hao, Xiuyuan Sun, Yingyu Chen, Xiaohui Liu, Yingjun Chang, Rong Jin, Hounan Wu, Qing Ge
Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4+ recent thymic emigrants (RTEs), and mature naive T cells in the periphery...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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