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https://www.readbyqxmd.com/read/28211007/daclizumab-a-review-in-relapsing-multiple-sclerosis
#1
Matt Shirley
Daclizumab (Zinbryta(®); previously known as daclizumab high-yield process) is a therapeutic monoclonal antibody that has recently been approved for the treatment of relapsing forms of multiple sclerosis (MS) in adults. Daclizumab is a humanized IgG1 monoclonal antibody directed against CD25, the alpha subunit of the high-affinity interleukin-2 receptor. As demonstrated in the phase III DECIDE trial, once-monthly subcutaneous daclizumab was superior to once-weekly intramuscular interferon (IFN) β-1a in reducing the clinical relapse rate and radiological measures of disease in patients with relapsing-remitting MS...
February 17, 2017: Drugs
https://www.readbyqxmd.com/read/28210072/the-parenteral-vitamin-c-improves-sepsis-and-sepsis-induced-multiple-organ-dysfunction-syndrome-via-preventing-cellular-immunosuppression
#2
Yu-Lei Gao, Bin Lu, Jian-Hua Zhai, Yan-Cun Liu, Hai-Xia Qi, Ying Yao, Yan-Fen Chai, Song-Tao Shou
Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo(-/-) mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells, as well as the organ functions, were determined...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28207945/cd4-cd25-garp-tregs-display-a-compromised-suppressive-function-in-patients-with-dilated-cardiomyopathy
#3
Yuzhen Wei, Kunwu Yu, Hui Wei, Xin Su, Ruirui Zhu, Huairui Shi, Haitao Sun, Quan Luo, Wenbin Xu, Junhui Xiao, Yucheng Zhong, Qiutang Zeng
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein -A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+) CD25(+) GARP(+) regulatory T cells (Tregs) in DCM. 45 DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral Th1 and Th17 number and their related cytokines (IFN-γ, IL-17), and an obvious decrease in Treg number, TGF-β1 levels and the expression of FOXP3 and GARP in patients with DCM as compared with controls...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28205525/testicular-activin-and-follistatin-levels-are-elevated-during-the-course-of-experimental-autoimmune-epididymo-orchitis-in-mice
#4
Nour Nicolas, Vera Michel, Sudhanshu Bhushan, Eva Wahle, Susan Hayward, Helen Ludlow, David M de Kretser, Kate L Loveland, Hans-Christian Schuppe, Andreas Meinhardt, Mark P Hedger, Monika Fijak
Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202745/plasma-levels-of-eicosapentaenoic-acid-are-associated-with-anti-tnf-responsiveness-in-rheumatoid-arthritis-and-inhibit-the-etanercept-driven-rise-in-th17-cell-differentiation-in-vitro
#5
Louisa Jeffery, Helena L Fisk, Philip C Calder, Andrew Filer, Karim Raza, Christopher D Buckley, Iain McInnes, Peter C Taylor, Benjamin A Fisher
OBJECTIVE: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation. METHODS: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured...
February 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28202460/t-regulatory-cells-and-dendritic-cells-protect-against-transfusion-related-acute-lung-injury-via-il-10
#6
Rick Kapur, Michael Kim, Rukhsana Aslam, Mark J McVey, Arata Tabuchi, Alice Luo, Jonathan Liu, Yuan Li, Shanjeevan Shanmugabhavananthan, Edwin R Speck, Anne Zufferey, George Yousef, Haibo Zhang, Mathew T Rondina, Andrew S Weyrich, Leendert Porcelijn, Wolfgang M Kuebler, Arthur S Slutsky, John W Semple
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by acute respiratory distress following blood transfusion. Donor antibodies are frequently involved, however, the pathogenesis and protective mechanisms in the recipient are poorly understood and specific therapies are lacking. Using newly developed murine TRALI models based on injection of anti-MHC class I antibodies, we found CD4+CD25+FoxP3+ T-regulatory cells (Tregs) and CD11c+ dendritic cells (DCs) to be critical effectors that protect against TRALI...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28198584/the-farming-environment-protects-mice-from-allergen-induced-skin-contact-hypersensitivity
#7
Christophe P Frossard, Vladimir Lazarevic, Nadia Gaïa, Stefano Leo, Camille Doras, Walid Habre, Jacques Schrenzel, Danielle Burger, Philippe A Eigenmann
BACKGROUND: Being born and raised in a farm provides a long-lasting protection for allergies. The microbial environment provided by farm animals is crucial to induce this protective effect, although underlying immune mechanisms remain elusive. OBJECTIVE: To establish a mouse model of global exposure to the farming environment and to study immunologic changes linked to protection of allergy. METHODS: Mice colonies were bred in parallel in a farm cowshed and the University animal facility (AF)...
February 15, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#8
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198394/cockroach-protease-allergen-induces-allergic-airway-inflammation-via-epithelial-cell-activation
#9
Sagar L Kale, Komal Agrawal, Shailendra Nath Gaur, Naveen Arora
Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197372/fam13a-is-associated-with-non-small-cell-lung-cancer-nsclc-progression-and-controls-tumor-cell-proliferation-and-survival
#10
Felix Eisenhut, Lisanne Heim, Sonja Trump, Susanne Mittler, Nina Sopel, Katerina Andreev, Fulvia Ferrazzi, Arif B Ekici, Ralf Rieker, Rebekka Springel, Vera L Assmann, Matthias Lechmann, Sonja Koch, Marina Engelhardt, Christina Warnecke, Denis I Trufa, Horia Sirbu, Arndt Hartmann, Susetta Finotto
Genome-wide association studies (GWAS) associated Family with sequence similarity 13, member A (FAM13A) with non-small cell lung cancer (NSCLC) occurrence. Here, we found increased numbers of FAM13A protein expressing cells in the tumoral region of lung tissues from a cohort of patients with NSCLC. Moreover, FAM13A inversely correlated with CTLA4 but directly correlated with HIF1α levels in the control region of these patients. Consistently, FAM13A RhoGAP was found to be associated with T cell effector molecules like HIF1α and Tbet and was downregulated in immunosuppressive CD4(+)CD25(+)Foxp3(+)CTLA4(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194759/association-of-peripheral-nk-cell-counts-with-helios-ifny-tregs-in-patients-with-good-long-term-renal-allograft-function
#11
Karina Trojan, Li Zhu, Mostafa Aly, Rolf Weimer, Nuray Bulut, Christian Morath, Gerhard Opelz, Volker Daniel
BACKGROUND: Little is known about a possible interaction of NK cells with Tregs in long-term stable kidney transplant recipients. METHODS: Absolute counts of lymphocyte and Treg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-color-fluorescence flow cytometry. Patients were 1946±2201 days (153-10268 days) posttransplant and showed a serum creatinine of 1.7±0.7 mg/dl. RESULTS: Renal transplant recipients investigated >1...
February 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28191775/noninvasive-assessment-of-an-engineered-bioactive-graft-in-myocardial-infarction-impact-on-cardiac-function-and-scar-healing
#12
Carolina Gálvez-Montón, Ramon Bragós, Carolina Soler-Botija, Idoia Díaz-Güemes, Cristina Prat-Vidal, Verónica Crisóstomo, Francisco M Sánchez-Margallo, Aida Llucià-Valldeperas, Paco Bogónez-Franco, Isaac Perea-Gil, Santiago Roura, Antoni Bayes-Genis
Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#13
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#14
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28183330/th17-and-cd24-hi-cd27-regulatory-b-lymphocytes-are-biomarkers-of-response-to-biologics-in-rheumatoid-arthritis
#15
Sarah Salomon, Caroline Guignant, Pierre Morel, Gauthier Flahaut, Clément Brault, Clément Gourguechon, Patrice Fardellone, Jean-Pierre Marolleau, Brigitte Gubler, Vincent Goëb
BACKGROUND: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28182700/pilot-double-blind-randomized-placebo-controlled-clinical-trial-of-the-supplement-food-nyaditum-resae%C3%A2-in-adults-with-or-without-latent-tb-infection-safety-and-immunogenicity
#16
Eva Montané, Ana Maria Barriocanal, Ana Lucía Arellano, Angelica Valderrama, Yolanda Sanz, Nuria Perez-Alvarez, Paula Cardona, Cristina Vilaplana, Pere-Joan Cardona
BACKGROUND: Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. METHODS: Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30)...
2017: PloS One
https://www.readbyqxmd.com/read/28176947/silencing-of-foxp3-enhances-the-antitumor-efficacy-of-gm-csf-genetically-modified-tumor-cell-vaccine-against-b16-melanoma
#17
Antonio Miguel, Luis Sendra, Verónica Noé, Carles J Ciudad, Francisco Dasí, David Hervas, María José Herrero, Salvador F Aliño
The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28176332/low-dose-interleukin-2-promotes-stat5-phosphorylation-treg-survival-and-ctla-4-dependent-function-in-autoimmune-liver-diseases
#18
Hannah C Jeffery, Louisa E Jeffery, Philipp Lutz, Margaret Corrigan, Gwilym J Webb, Gideon M Hirschfield, David H Adams, Ye Htun Oo
CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and regulatory T cells contribute to the pathogenesis of autoimmune diseases. We recently reported that the hepatic microenvironment is deficient in IL-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate STAT5 phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases...
February 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28176275/reduced-activated-t-lymphocytes-cd4-cd25-and-plasma-levels-of-cytokines-in-parkinson-s-disease
#19
Natalia Pessoa Rocha, Frankcinéia Assis, Paula Luciana Scalzo, Érica Leandro Marciano Vieira, Izabela Guimarães Barbosa, Mariana Soares de Souza, Paulo Pereira Christo, Helton José Reis, Antonio Lucio Teixeira
Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses...
February 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28174597/cd4%C3%A2-%C3%A2-cd25%C3%A2-%C3%A2-cd127-high-cells-as-a-negative-predictor-of-multiple-organ-failure-in-acute-pancreatitis
#20
Wei Wang, He-Ping Xiang, Hui-Ping Wang, Li-Xin Zhu, Xiao-Ping Geng
BACKGROUND: It has been suggested that severity of the immune response induced by immune cells is associated with morbidity and mortality from acute pancreatitis. The authors investigated and evaluated the relationship between distinct peripheral lymphocyte subsets at admission and clinical outcome prior to hospital discharge so as to find a predictor to the prognosis of acute pancreatitis in lymphocyte profile. METHODS: Lymphocyte subsets in admission peripheral venous blood were tested through flow cytometry on 48 patients with acute pancreatitis...
2017: World Journal of Emergency Surgery: WJES
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