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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/28527402/a-rare-e13a3-b2a3-bcr-abl1-fusion-transcript-with-normal-karyotype-in-chronic-myeloid-leukemia-the-challenges-in-diagnosis-and-monitoring-minimal-residual-disease-mrd
#1
M-H Duan, H Li, H Cai
Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28521800/immunogenicity-and-immunomodulatory-effects-of-the-human-chondrocytes-hchonj
#2
Chae-Lyul Lim, Yeon-Ju Lee, Jong-Ho Cho, Heonsik Choi, Bumsup Lee, Myung Chul Lee, Sujeong Kim
BACKGROUND: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells...
May 18, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#3
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/28508945/clinical-efficacy-of-percutaneous-cryoablation-combined-with-allogenic-nk-cell-immunotherapy-for-advanced-non-small-cell-lung-cancer
#4
Mao Lin, Shu-Zhen Liang, Xiao-Hua Wang, Ying-Qing Liang, Ming-Jie Zhang, Li-Zhi Niu, Ji-Bing Chen, Hai-Bo Li, Ke-Cheng Xu
In this study, the safety and clinical efficacy of cryosurgery combined with allogenic NK cell immunotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) were evaluated. From July 2016 to March 2017, we enrolled 60 patients who met the enrollment criteria and divided them into two groups: (1) the simple cryoablation group (n = 30) and (2) the cryoablation combined with allogenic NK cell group (n = 30). The changes in immune function, quality of life, and clinical response were evaluated...
May 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28505516/induction-of-experimental-autoimmune-orchitis-by-immunization-with-xenogenic-testicular-germ-cells-in-mice
#5
Ning Qu, Hayato Terayama, Yoshie Hirayanagi, Miyuki Kuramasu, Yuki Ogawa, Shogo Hayashi, Shuichi Hirai, Munekazu Naito, Masahiro Itoh
We previously showed that immunization of mice with syngeneic or allogeneic testicular germ cells (TGC) alone induces autoimmune inflammation in the testes without using any adjuvant. In the present study, we examined testicular autoimmune response against xenogenic TGC antigens in mice. The mice were immunized with murine, rat or guinea pig TGC and then the histopathology, delayed type hypersensitivity (DTH) response and humoral autoimmunity were investigated. The results showed that immunization with not only murine but also rat TGC caused experimental autoimmune orchitis (EAO) with hypospermatogenesis in mice, while that with guinea pig TGC could not...
April 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28504860/allogeneic-bone-marrow-derived-mesenchymal-stromal-cells-expanded-in-vitro-for-treatment-of-aplastic-anemia-a-multicenter-phase-ii-trial
#6
Yan Pang, Hao-Wen Xiao, Hang Zhang, Zeng-Hui Liu, Li Li, Yang Gao, Hong-Bo Li, Zu-Jun Jiang, Huo Tan, Jing-Ren Lin, Xin Du, Jian-Yu Weng, Da-Nian Nie, Dong-Jun Lin, Xiang-Zhong Zhang, Qi-Fa Liu, Duo-Rong Xu, Hai-Jia Chen, Xiao-Hu Ge, Xiao-Yan Wang, Yang Xiao
We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogeneic BM-MSCs at a dose of 1-2 × 10(6) cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions...
May 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#7
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28502902/retinoic-acid-mediated-anti-inflammatory-responses-in-equine-immune-cells-stimulated-by-lps-and-allogeneic-mesenchymal-stem-cells
#8
Leila Abdelhamid, Hayam Hussein, Mostafa Ghanem, Nour Eissa
Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)-based therapy is an effective approach to induce tissue healing and regeneration in many equine orthopedic conditions. However, MSCs-based therapies induced inflammatory responses in vivo. This study aimed to: 1. Determine the effect of RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)- and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs)...
May 5, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28502825/treatment-of-severe-forms-of-lps-responsive-beige-like-anchor-protein-lrba-deficiency-by-allogeneic-hematopoietic-stem-cell-transplantation
#9
Markus G Seidel, Katrin Böhm, Figen Dogu, Austen Worth, Adrian Thrasher, Benoit Florkin, Aydan İkincioğulları, Anke Peters, Shahrzad Bakhtiar, Marie Meeths, Polina Stepensky, Isabelle Meyts, Svetlana O Sharapova, Laura Gámez-Díaz, Lennart Hammarström, Stephan Ehl, Bodo Grimbacher, Andrew R Gennery
LRBA deficiency, a life-threatening immunodeficiency/autoimmunity disorder, was treated by HSCT in 12 patients, four of whom died from transplant-related causes. Six patients were cured without further need of immunosuppression, and two are in partial remission.
May 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28502334/ap-1-expression-and-its-clinical-relevance-in-immune-disorders-and-cancer
#10
REVIEW
Shivtia Trop-Steinberg, Yehudit Azar
The inflammatory response is known to have a significant role in certain autoimmune diseases and malignancies. We review current knowledge regarding the functions of activator protein 1 (AP-1) as an important modulator in several immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis and in long-term allogeneic hematopoietic stem cell transplantation survivors; however, decreased expression of AP-1 has been observed in psoriasis, systematic lupus erythematosus and in patients who do not survive after hematopoietic stem cell transplantation...
May 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28499587/the-phosphodiesterase-4-inhibitor-apremilast-inhibits-th1-but-promotes-th17-responses-induced-by-6-sulfo-lacnac-slan-dendritic-cells
#11
Stephanie Oehrl, Hridayesh Prakash, Annette Ebling, Nina Trenkler, Priscila Wölbing, Anja Kunze, Thomas Döbel, Marc Schmitz, Alexander Enk, Knut Schäkel
BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs...
April 20, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28495641/safety-and-efficacy-of-infliximab-therapy-in-the-setting-of-steroid-refractory-acute-graft-versus-host-disease
#12
Fevzi F Yalniz, Mehrdad Hefazi, Kristen McCollough, Mark R Litzow, William J Hogan, Robert Wolf, Hassan Alkhateeb, Ankit Kansagra, Moussab Damlaj, Mrinal M Patnaik
Acute graft versus host disease (aGVHD) is the leading cause of morbidity and mortality following allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first line treatment; however, less than half of the patients achieve durable remissions. Studies suggest that tumor necrosis factor alpha (TNF-α), a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-tumor necrosis factor alpha (TNF-α) therapy with infliximab in 35 patients with steroid refractory aGVHD (SR-aGVHD)...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28495143/central-and-peripheral-nervous-system-immune-mediated-demyelinating-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
M I Stefanou, F Bischof
OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients. BACKGROUND: CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent. METHODS: Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28494518/correlates-of-resistance-and-relapse-during-blinatumomab-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia
#14
Ibrahim Aldoss, Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts >50%) (P=0.02), history of prior EM-ALL (P=0...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28489338/regulatory-t-cells-promote-natural-killer-cell-education-in-mixed-chimeras
#15
Benedikt Mahr, Nina Pilat, Svenja Maschke, Nicolas Granofszky, Christoph Schwarz, Lukas Unger, Karin Hock, Andreas M Farkas, Christoph Klaus, Heinz Regele, Thomas Wekerle
Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in non-irradiated recipient mice conditioned with costimulation blockade and mTOR inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation (BMT) led to BM engraftment and persistent chimerism without Treg transfer, but failed to induce skin graft tolerance...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28487696/natural-killer-cells-in-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#16
REVIEW
Federico Simonetta, Maite Alvarez, Robert S Negrin
Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487694/human-bronchial-epithelial-cells-induce-cd141-cd123-dc-sign-flt3-monocytes-that-promote-allogeneic-th17-differentiation
#17
Amiq Gazdhar, Fabian Blank, Valerie Cesson, Alban Lovis, John David Aubert, Romain Lazor, Francois Spertini, Anne Wilson, Katrin Hostettler, Laurent P Nicod, Carolina Obregon
Little is known about monocyte differentiation in the lung mucosal environment and about how the epithelium shapes monocyte function. We studied the role of the soluble component of bronchial epithelial cells (BECs) obtained under basal culture conditions in innate and adaptive monocyte responses. Monocytes cultured in bronchial epithelial cell-conditioned media (BEC-CM) specifically upregulate CD141, CD123, and DC-SIGN surface levels and FLT3 expression, as well as the release of IL-1β, IL-6, and IL-10. BEC-conditioned monocytes stimulate naive T cells to produce IL-17 through IL-1β mechanism and also trigger IL-10 production by memory T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28486431/mesenchymal-stem-cell-derived-extracellular-vesicles-a-role-in-hematopoietic-transplantation
#18
REVIEW
Luciana De Luca, Stefania Trino, Ilaria Laurenzana, Daniela Lamorte, Antonella Caivano, Luigi Del Vecchio, Pellegrino Musto
Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28485720/herpesvirus-micrornas-for-use-in-gene-therapy-immune-evasion-strategies
#19
REVIEW
S T F Bots, R C Hoeben
Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require life-long treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system...
May 9, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28484169/current-diagnosis-and-treatment-for-myelodysplastc-syndromes
#20
Tomoko Hata
Genetic analysis of myelodysplastic syndrome (MDS) using next-generation sequencing yields medcially important information, showing gene mutations in 90% of MDS cases. The World Health Organization (WHO) classification was revised in 2016 to incorporate SF3B1 gene mutations, frequently seen in MDS with ringed sideroblasts, into the diagnostic criteria. Unlike the poor prognosis seen in cases with ASXL1, EZH2, RUNX1 and in particular, TP53 MDS-related mutations, SF3B1 gene mutations show a favorable prognosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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