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https://www.readbyqxmd.com/read/27911424/-effectiveness-of-soft-contact-lenses-in-severe-keratoconjunctivitis-sicca-treated-with-local-immunosuppressive-therapy
#1
T N Safonova, O V Gladkova, V I Boev, A A Fedorov
AIM: To study the effectiveness of soft contact lenses in severe keratoconjunctivitis sicca (KCS) treated with local immunosuppressive therapy. MATERIAL AND METHODS: We have examined 41 patients (60 eyes) with severe KCS, including 3 men (4 eyes) and 38 women (56 eyes) aged from 27 to 76 years. Group 1 consisted of 22 persons (30 eyes) who were prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 consisted of 19 patients (30 eyes) who received instillations of cyclosporine А 0...
2016: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#2
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911367/a-simple-fluorescence-assay-for-quantification-of-canine-neutrophil-extracellular-trap-release
#3
Unity Jeffery, Robert D Gray, Dana N LeVine
Neutrophil extracellular traps are networks of DNA, histones and neutrophil proteins released in response to infectious and inflammatory stimuli. Although a component of the innate immune response, NETs are implicated in a range of disease processes including autoimmunity and thrombosis. This protocol describes a simple method for canine neutrophil isolation and quantification of NETs using a microplate fluorescence assay. Blood is collected using conventional venipuncture techniques. Neutrophils are isolated using dextran sedimentation and a density gradient using conditions optimized for dog blood...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910962/baricitinib-jak-inhibition-for-rheumatoid-arthritis
#4
J Gras
Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease characterized by inflammation and joint destruction, is associated with pain, progressive disability, systemic comorbidities and early death. Conventional disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs (bDMARDs) have been able to achieve remission or a very low disease activity status for RA. Nevertheless, since many patients do not reach a sufficient response with DMARDs or present with unacceptable side effects, new therapies are needed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910766/natural-igm-and-the-development-of-b-cell-mediated-autoimmune-diseases
#5
Trang T T Nguyen, Nicole Baumgarth
Most serum immunoglobulin M (IgM) is "natural IgM", which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self- and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27909795/altered-gut-microbiota-in-ra-implications-for-treatment
#6
Y Kang, Y Cai, X Zhang, X Kong, J Su
Rheumatoid arthritis (RA) is an autoimmune disease with progressive joint disorder. The complex interplay of genetic and environmental influences is important for the development of the disease. A growing body of evidence has shed light on the association of dysbiosis of gut microbiota with RA. Certain gut microbial strains have been shown to inhibit or attenuate immune responses in RA experimental models, suggesting that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of RA...
December 1, 2016: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/27909439/the-a-allele-of-the-single-nucleotide-polymorphism-rs630923-creates-a-binding-site-for-mef2c-resulting-in-reduced-cxcr5-promoter-activity-in-b-cell-lymphoblastic-cell-lines
#7
Nikita A Mitkin, Alisa M Muratova, Anton M Schwartz, Dmitry V Kuprash
Chemokine receptor CXCR5 is highly expressed in B-cells and under normal conditions is involved in their migration to specific areas of secondary lymphoid organs. B-cells are known to play an important role in various autoimmune diseases including multiple sclerosis (MS) where areas of demyelinating lesions attract B-cells by overexpressing CXCL13, the CXCR5 ligand. In this study, we aimed to determine the functional significance of single-nucleotide polymorphism rs630923 (A/C), which is located in cxcr5 gene promoter, and its common allele is associated with increased risk of MS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909437/differentially-methylated-dna-regions-in-monozygotic-twin-pairs-discordant-for-rheumatoid-arthritis-an-epigenome-wide-study
#8
Anders J Svendsen, Kristina Gervin, Robert Lyle, Lene Christiansen, Kirsten Kyvik, Peter Junker, Christian Nielsen, Gunnar Houen, Qihua Tan
OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909192/the-more-the-merrier-scoring-statistics-and-animal-welfare-in-experimental-autoimmune-encephalomyelitis
#9
Pushpalatha Palle, Filipa M Ferreira, Axel Methner, Thorsten Buch
Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants...
December 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27909160/evaluation-of-polymorphic-variants-in-apoptotic-genes-and-their-role-in-susceptibility-and-clinical-progression-to-systemic-lupus-erythematosus
#10
N Glesse, P Vianna, L M G Paim, M C C Matte, A K K Aguiar, P L Palhano, O A Monticielo, C V Brenol, R M Xavier, J A B Chies
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes...
November 30, 2016: Lupus
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#11
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909056/interferons-induce-expression-of-samhd1-in-monocytes-through-downregulation-of-mir-181a-and-mir-30a
#12
Maximilan Riess, Nina V Fuchs, Adam Idica, Matthias Hamdorf, Egbert Flory, Irene Munk Pedersen, Renate König
SAMHD1 is a phosphohydrolase maintaining cellular dNTP homeostasis but also acts as a critical regulator in innate immune responses due to its antiviral activity and association with autoimmune disease leading to aberrant activation of interferon. SAMHD1 expression is differentially regulated by interferon in certain primary cells, but the underlying mechanism is not understood. Here, we report a detailed characterization of the promotor region, the 5' and 3' untranslated region (UTR) of SAMHD1, and the mechanism responsible for the cell-type dependent upregulation of SAMHD1 protein by interferon...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908935/posttranslational-regulation-of-smads
#13
REVIEW
Pinglong Xu, Xia Lin, Xin-Hua Feng
Transforming growth factor β (TGF-β) family signaling dictates highly complex programs of gene expression responses, which are extensively regulated at multiple levels and vary depending on the physiological context. The formation, activation, and destruction of two major functional complexes in the TGF-β signaling pathway (i.e., the TGF-β receptor complexes and the Smad complexes that act as central mediators of TGF-β signaling) are direct targets for posttranslational regulation. Dysfunction of these complexes often leads or contributes to pathogenesis in cancer and fibrosis and in cardiovascular, and autoimmune diseases...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27908754/cyclic-citrullinated-mbp87-99-peptide-stimulates-t-cell-responses-implications-in-triggering-disease
#14
Vasso Apostolopoulos, George Deraos, Minos-Timotheos Matsoukas, Stephanie Day, Lily Stojanovska, Theodore Tselios, Maria-Eleni Androutsou, John Matsoukas
Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K(91),P(96) (TCR contact residues) to R(91),A(96); [R(91),A(96)]MBP87-99) results in altered T cell responses and inhibits EAE symptoms...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908532/ram-589-555-a-new-polymerase-1-inhibitor-as-innovative-targeted-treatment-for-multiple-sclerosis
#15
A Achiron, R Zilkha-Falb, R Mashiach, M Gurevich
Targeting Polymerase-1 (POL1) transcription machinery is a new strategy for suppression of multiple sclerosis (MS) disease activity that is based on suppression of ribosomal biogenesis and subsequent activation of apoptosis. We developed an oral POL1 inhibiting compound RAM-589.555, that suppress ribosomal biogenesis as an innovative therapeutic approach to ameliorate MS. RAM-589.555 shows high permeability, specificity to POL1 pathway, ability to induce apoptosis and to inhibit proliferation and viability of activated lymphocytes both in-vitro and in-vivo...
November 17, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27908520/diagnosis-and-updates-in-celiac-disease
#16
REVIEW
Sarah Shannahan, Daniel A Leffler
Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods...
January 2017: Gastrointestinal Endoscopy Clinics of North America
https://www.readbyqxmd.com/read/27907250/the-transcriptional-co-activator-bob1-is-associated-with-pathologic-b-cell-responses-in-autoimmune-tissue-inflammation
#17
Maria J Levels, Melissa N Van Tok, Tineke Cantaert, Juan D Cañete, Frans G M Kroese, Kristine Germar, Hergen Spits, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. In this study we aimed to identify molecular switches controlling pathological B cell responses in rheumatoid arthritis (RA). METHODS: Candidate molecules were identified by gene expression profiling of RA synovitis and validated by qPCR and immunohistochemistry. B cell-specific expression was confirmed by immunofluorescence, immunoblotting and flow cytometry...
December 1, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27907119/gray-matter-hypoxia-in-the-brain-of-the-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#18
Thomas W Johnson, Ying Wu, Nabeela Nathoo, James A Rogers, V Wee Yong, Jeff F Dunn
BACKGROUND: Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS. OBJECTIVE: Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course...
2016: PloS One
https://www.readbyqxmd.com/read/27906879/presence-of-organ%C3%A2-specific-antibodies-in-patients-with-systemic-sclerosis
#19
Ewa Wielosz, Maria Majdan, Arkadiusz Koszarny, Magdalena Dryglewska, Jacek Tabarkiewicz
INTRODUCTION According to the literature, organ‑specific antibodies may be present in the course of systemic sclerosis (SSc). OBJECTIVES The aim of this study was to assess the prevalence of antithyroid antibodies (antithyroid peroxidase antibodies [anti‑TPO] and antithyroglobulin antibodies) and of antimitochondrial antibodies (AMAs), as well as to evaluate their clinical significance in patients with SSc. PATIENTS AND METHODS The study involved 86 consecutive in‑hospital patients with SSc (32 patients with diffuse cutaneous SSc [dcSSc] and 54 with limited cutaneous SSc [lcSSc])...
October 5, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27906864/potential-for-treatment-and-a-zika-virus-vaccine
#20
Natalie Quanquin, Lulan Wang, Genhong Cheng
PURPOSE OF REVIEW: Zika virus (ZIKV) has only recently been exposed as a significant public health threat, and much of our limited knowledge of its pathogenesis and triggered immune responses were discovered in only the last few years. There are currently no ZIKV-specific therapeutics or vaccines available. This review seeks to bring the reader up-to-date with the latest developments in finding a way to combat this emerging infectious disease. RECENT FINDINGS: Current strategies used for developing ZIKV vaccines or treatments follow proven methods used against other flaviviruses...
November 30, 2016: Current Opinion in Pediatrics
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