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Jennifer K Roe, Niclas Thomas, Eliza Gil, Katharine Best, Evdokia Tsaliki, Stephen Morris-Jones, Sian Stafford, Nandi Simpson, Karolina D Witt, Benjamin Chain, Robert F Miller, Adrian Martineau, Mahdad Noursadeghi
BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB...
October 6, 2016: JCI Insight
Chiara Cordiglieri, Fulvio Baggi, Pia Bernasconi, Dimos Kapetis, Elisa Faggiani, Alessandra Consonni, Francesca Andreetta, Rita Frangiamore, Paolo Confalonieri, Carlo Antozzi, Renato Mantegazza
Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β...
October 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Daniel Muthas, Anna Reznichenko, Clare A Balendran, Gerhard Böttcher, Ib Groth Clausen, Carina Kärrman Mårdh, Tomas Ottosson, Mohib Uddin, Thomas T MacDonald, Silvio Danese, Mark Berner Hansen
OBJECTIVES: This review article describes the role of neutrophils in mucosal injury and the resulting crypt abscesses characteristic of ulcerative colitis. We also review selected biomarkers for monitoring neutrophil presence and activity in the mucosa as well as their potential as therapeutic targets. MATERIAL: We have collated and selectively reviewed data on the most prominent well-established and emerging neutrophil-related biomarkers and potential therapeutic targets (calprotectin, lactoferrin, CXCR1, CXCR2, MMP-9, NGAL, elafin, HNE, pANCAs, MPO, CD16, CD177, CD64, HNPs, SLPI and PTX3) in ulcerative colitis...
September 9, 2016: Scandinavian Journal of Gastroenterology
Julie Demaret, Fabienne Venet, Jonathan Plassais, Marie-Angélique Cazalis, Hélène Vallin, Arnaud Friggeri, Alain Lepape, Thomas Rimmelé, Julien Textoris, Guillaume Monneret
Sepsis represents the host's systemic inflammatory response to an infection. In this condition, immune response associates a marked inflammatory response and the delayed development of severe dysfunctions affecting both innate and adaptive responses. As neutrophils are the first line of defense against infection, they are central to the pathophysiology of sepsis in first hours. Nevertheless, their role during immunosuppression phase remains elusive. The main objective of the current work was to perform a transcriptomic study on purified neutrophils from septic shock patients (n=9) so as to identify genes that are differentially expressed during the first week after disease onset both (3-4 and 6-8days) versus healthy donors...
October 2016: Immunology Letters
Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno
We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7...
2016: Cancer Informatics
Behnaz Bayat, Gregor Bein, Ulrich J Sachs
BACKGROUND: Human neutrophil antigen-2 is located on a glycosylphosphatidylinositol-anchored receptor, CD177. Humans not expressing CD177 on their neutrophils may, under defined conditions, form isoantibodies. The genetic background for the absence of CD177 is not fully understood, and genetic screening of patients and donors is currently unavailable. A recent study has documented two mutations associated with CD177 absence: a nonsense polymorphism c.843A>T and a single-base deletion c...
August 2016: Transfusion
Adrian Schreiber, Claudia Eulenberg-Gustavus, Astrid Bergmann, Uwe Jerke, Ralph Kettritz
ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than with MPO as the neutrophil-specific CD177 receptor is involved in PR3 surface expression and PR3-ANCA-induced neutrophil activation. Modeling human disease is important to clinical research. Highly successful mouse models of MPO-ANCA vasculitis exist; however, recapitulating PR3-ANCA vasculitis has not been successful...
June 30, 2016: Journal of Leukocyte Biology
M Port, F Herodin, M Valente, M Drouet, A Lamkowski, M Majewski, M Abend
We implemented a two-stage study to predict late occurring hematologic acute radiation syndrome (HARS) in a baboon model based on gene expression changes measured in peripheral blood within the first two days after irradiation. Eighteen baboons were irradiated to simulate different patterns of partial-body and total-body exposure, which corresponded to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS...
July 2016: Radiation Research
Zuopeng Wu, Rong Liang, Thomas Ohnesorg, Vicky Cho, Wesley Lam, Walter P Abhayaratna, Paul A Gatenby, Chandima Perera, Yafei Zhang, Belinda Whittle, Andrew Sinclair, Christopher C Goodnow, Matthew Field, T Daniel Andrews, Matthew C Cook
Most humans harbor both CD177neg and CD177pos neutrophils but 1-10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion...
May 2016: PLoS Genetics
Denis Maenner, Silke Werth, Gregor Bein, Sentot Santoso
Generally, B-cell responses against human platelet antigens are assessed by the serological detection of specific platelet antibodies, mostly against β3 integrin. However, this approach seems to be of low sensitivity, since platelet autoantibodies against αIIbβ3 are detected in only 50% of all patients with immune thrombocytopenia (ITP). In this study, a novel B-cell ELIspot method was established to characterize the specificity of mouse monoclonal antibodies (moabs) against human β3 integrin. Moabs produced by hybridomas were immobilized on membrane and bound antibodies were visualized as spots using biotinylated recombinant proteins αIIbβ3 or αvβ3 and the enzyme labeled streptavidin-substrate system...
May 16, 2016: Platelets
Zhan Zhang, Xinyue Wu, Shuyuan Cao, Li Wang, Di Wang, Hui Yang, Yiming Feng, Shoulin Wang, Lei Li
Emerging evidence shows that dietary agents and phytochemicals contribute to the prevention and treatment of ulcerative colitis (UC). We first reported the effects of dietary caffeic acid (CaA) on murine experimental colitis and on fecal microbiota. Colitis was induced in C57BL/6 mice by administration of 2.5% dextran sulfate sodium (DSS). Mice were fed a control diet or diet with CaA (1 mM). Our results showed that dietary CaA exerted anti-inflammatory effects in DSS colitis mice. Moreover, CaA could significantly suppress the secretion of IL-6, TNFα, and IFNγ and the colonic infiltration of CD3+ T cells, CD177+ neutrophils and F4/80+ macrophages via inhibition of the activation of NF-κB signaling pathway...
May 31, 2016: Oncotarget
Adrian Schreiber, Alexandra Jannerjahn, Ralph Kettritz
No abstract text is available yet for this article.
2015: Immunohematology
Eóin C O'Brien, Wayel H Abdulahad, Abraham Rutgers, Minke G Huitema, Vincent P O'Reilly, Alice M Coughlan, Mark Harrington, Peter Heeringa, Mark A Little, Fionnuala B Hickey
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells...
2015: Scientific Reports
Yunfang Li, David C Mair, Randy M Schuller, Ling Li, Jianming Wu
Human neutrophil antigen 2 (HNA-2) deficiency is a common phenotype as 3-5% humans do not express HNA-2. HNA-2 is coded by CD177 gene that associates with human myeloproliferative disorders. HNA-2 deficient individuals are prone to produce HNA-2 alloantibodies that cause a number of disorders including transfusion-related acute lung injury and immune neutropenia. In addition, the percentages of HNA-2 positive neutrophils vary significantly among individuals and HNA-2 expression variations play a role in human diseases such as myelodysplastic syndrome, chronic myelogenous leukemia, and gastric cancer...
May 2015: PLoS Genetics
Benedicto Crespo-Facorro, Carlos Prieto, Jesus Sainz
BACKGROUND: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. METHODS: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. RESULTS: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0...
February 2015: International Journal of Neuropsychopharmacology
Loes E M Kistemaker, Ronald P van Os, Albertina Dethmers-Ausema, I Sophie T Bos, Machteld N Hylkema, Maarten van den Berge, Pieter S Hiemstra, Jürgen Wess, Herman Meurs, Huib A M Kerstjens, Reinoud Gosens
Anticholinergics, blocking the muscarinic M3 receptor, are effective bronchodilators for patients with chronic obstructive pulmonary disease. Recent evidence from M(3) receptor-deficient mice (M(3)R(-/-)) indicates that M3 receptors also regulate neutrophilic inflammation in response to cigarette smoke (CS). M(3) receptors are present on almost all cell types, and in this study we investigated the relative contribution of M(3) receptors on structural cells vs. inflammatory cells to CS-induced inflammation using bone marrow chimeric mice...
January 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Qing Xie, Julia Klesney-Tait, Kathy Keck, Corey Parlet, Nicholas Borcherding, Ryan Kolb, Wei Li, Lorraine Tygrett, Thomas Waldschmidt, Alicia Olivier, Songhai Chen, Guang-Hui Liu, Xiangrui Li, Weizhou Zhang
Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAM1. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregulated following endotoxin exposure...
February 2015: Protein & Cell
Jennifer M Cole, Stancy Joseph, Christopher G Sudhahar, Karen D Cowden Dahl
Cancer stem cells (CSCs) are defined as a subset of slow cycling and undifferentiated cells that divide asymmetrically to generate highly proliferative, invasive, and chemoresistant tumor cells. Therefore, CSCs are an attractive population of cells to target therapeutically. CSCs are predicted to contribute to a number of types of malignancies including those in the blood, brain, lung, gastrointestinal tract, prostate, and ovary. Isolating and enriching a tumor cell population for CSCs will enable researchers to study the properties, genetics, and therapeutic response of CSCs...
2014: Journal of Visualized Experiments: JoVE
Carlos Ramirez-Velazquez, Nonantzin Beristain-Covarrubias, Leopoldo Guido-Bayardo, Vianney Ortiz-Navarrete
BACKGROUND: Class-I MHC-restricted T cell-associated molecule (CRTAM) is a protein expressed by activated natural killer T (NKT) cells, natural killer (NK) cells, CD8 T cells, and certain CD4 T lymphocytes. It is also expressed in Purkinje neurons and epithelial cells. However, no studies have examined the expression of CRTAM in peripheral blood cells during homeostasis or disease. Therefore, we explored whether CRTAM expression is influenced by the presence of allergic asthma. METHODS: We collected whole peripheral blood cells from non-asthmatic control subjects (n = 17) and patients with asthma (n = 17)...
2014: Allergy, Asthma, and Clinical Immunology
Nan Hu, Helena Mora-Jensen, Kim Theilgaard-Mönch, Berber Doornbos-van der Meer, Minke G Huitema, Coen A Stegeman, Peter Heeringa, Cees G M Kallenberg, Johanna Westra
OBJECTIVE: Differential gene expression in CD177+ and CD177- neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). METHODS: Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177- subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips...
2014: PloS One
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