Read by QxMD icon Read

interferon type I AND SLE

Bo Chen, Katherine A Vousden, Brian Naiman, Sean Turman, Hong Sun, Shu Wang, Lisa M K Vinall, Benjamin P Kemp, Srinath Kasturiangan, D Gareth Rees, Ethan Grant, Mary Jane Hinrichs, Steven Eck, Antonio DiGiandomenico, M Jack Borrok, Martin J Borrok, Neang Ly, Ximing Xiong, Carlos Gonzalez, Christopher Morehouse, Yue Wang, Yebin Zhou, Jennifer Cann, Weiguang Zhao, Holly Koelkebeck, Koshu Okubo, Tanya N Mayadas, David Howe, Janet Griffiths, Roland Kolbeck, Ronald Herbst, Gary P Sims
OBJECTIVE: Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim of this study was to generate and characterise a first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. METHODS: VIB9600 was humanised and optimised from the IV.3 Ab. Binding affinity and specificity were determined by Biacore and ELISA. Confocal microscopy, Flow Cytometry-based assays and binding competition assays were used to assess the mode of action of the antibody...
November 20, 2018: Annals of the Rheumatic Diseases
Andrea Fava, Michelle Petri
Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogenous, reflecting the complex mosaic of disrupted molecular pathways converging into the SLE clinical phenotype. The SLE complex pathogenesis involves multiple cellular components of the innate and immune systems, presence of autoantibodies and immunocomplexes, engagement of the complement system, dysregulation of several cytokines including type I interferons, and disruption of the clearance of nucleic acids after cell death...
November 15, 2018: Journal of Autoimmunity
Colleen S Curran, Sarthak Gupta, Ignacio Sanz, Elad Sharon
Programmed death (PD)-1 receptors and their ligands have been identified in the pathogenesis and development of systemic lupus erythematosus (SLE). Two key pathways, toll-like receptor and type I interferon, are significant to SLE pathogenesis and modulate the expression of PD-1 and the ligands (PD-L1, PD-L2) through activation of NF-κB and/or STAT1. These cell signals are regulated by tyrosine kinase (Tyro, Axl, Mer) receptors (TAMs) that are aberrantly activated in SLE. STAT1 and NF-κB also exhibit crosstalk with the aryl hydrocarbon receptor (AHR)...
November 2, 2018: Journal of Autoimmunity
Li Zheng, Hao Zhang, Youzhou Tang
Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organs involved. Kidney damage is common among SLE patients. In lupus nephritis, extracellular DNA accumulation from necrosis cells and activated cells is perceived as initial step of inflammation. The up-regulated type I IFN is one pivotal cytokine causing downstream inflammation enlargement. Currently, intracellular DNA sensor cGAS signaling has been found to be related to lupus nephritis and the aberrant up-regulation of type I IFN...
December 2018: Medical Hypotheses
Stancy Joseph, Nysia I George, Bridgett Green-Knox, Edward L Treadwell, Beverly Word, Sarah Yim, Beverly Lyn-Cook
Systemic lupus erythematosus (SLE or lupus) is a heterogeneous autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. DNA methylation plays an important role in the pathogenesis of lupus. We have performed an epigenome-wide DNA methylation study in lupus and healthy control (non-lupus) subjects to identify epigenetic patterns in lupus characterized ethnicity and SLE disease activity index (SLEDAI). A total of fifty-seven lupus patients (39 African American (AA) and 18 European American (EA)) and 33 healthy controls (17 AA and 16 EA) were studied...
October 6, 2018: Journal of Autoimmunity
Michelle L Ratliff, Joshua Garton, Lori Garman, M David Barron, Constantin Georgescu, Kathryn A White, Eliza Chakravarty, Jonathan D Wren, Courtney G Montgomery, Judith A James, Carol F Webb
Type I interferons (IFN) causes inflammatory responses to pathogens, and can be elevated in autoimmune diseases such as systemic lupus erythematosus (SLE). We previously reported unexpected associations of increased numbers of B lymphocytes expressing the DNA-binding protein ARID3a with both IFN alpha (IFNα) expression and increased disease activity in SLE. Here, we determined that IFNα producing low density neutrophils (LDNs) and plasmacytoid dendritic cells (pDCs) from SLE patients exhibit strong associations between ARID3a protein expression and IFNα production...
October 5, 2018: Journal of Autoimmunity
Allison Sang, Thomas Danhorn, Jacob N Peterson, Andrew L Rankin, Brian P O'Connor, Sonia M Leach, Raul M Torres, Roberta Pelanda
Autoreactive B cells have a major function in autoimmunity. A small subset of B cells expressing two distinct B-cell-antigen-receptors (B2R cells) is elevated in many patients with systematic lupus erythematosus (SLE) and in the MRL(/lpr) mouse model of lupus, and is often autoreactive. Here we show, using RNAseq and in vitro and in vivo analyses, signals that are required for promoting B2R cell numbers and effector function in autoimmune mice. Compared with conventional B cells, B2R cells are more responsive to Toll-like receptor 7/9 and type I/II interferon treatment, display higher levels of MHCII and co-receptors, and depend on IL-21 for their homeostasis; moreover they expand better upon T cell-dependent antigen stimulation, and mount a more robust memory response, which are characteristics essential for enhanced (auto)immune responses...
September 28, 2018: Nature Communications
Kei Sakata, Shingo Nakayamada, Yusuke Miyazaki, Satoshi Kubo, Akina Ishii, Kazuhisa Nakano, Yoshiya Tanaka
Objectives: Aberrant and persistent production of interferon-α (IFN-α) by plasmacytoid dendritic cells (pDCs) is known to play a key role in the pathogenesis of systemic lupus erythematosus (SLE). To assess the precise function of pDCs in SLE patients, we investigated the differential regulation of Toll-like receptor 7 (TLR7) and TLR9 responses during IFN-α production by pDCs. Methods: Peripheral blood mononuclear cells (PBMCs) in SLE patients without hydroxychloroquine treatment, rheumatoid arthritis patients and heathy controls were stimulated with TLR7 and TLR9 agonists...
2018: Frontiers in Immunology
Christina Adamichou, Spyros Georgakis, George Bertsias
Despite advancements in the care of lupus nephritis, a considerable proportion of patients may respond poorly or flare while on conventional immunosuppressive agents. Studies in murine and human lupus have illustrated a pathogenic role for several cytokines by enhancing T- and B-cell activation, autoantibodies production and affecting the function of kidney resident cells, therefore supporting their potential therapeutic targeting. To this end, there is limited post-hoc randomized evidence to suggest beneficial effect of belimumab, administered on top of standard-of-care, during maintenance therapy in lupus nephritis...
September 2, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Maurer Kelly, Shi Lihua, Zhang Zhe, Song Li, Paucar Yoselin, Petri Michelle, E Sullivan Kathleen
Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons...
December 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Linyu Geng, Shiying Wang, Xia Li, Dandan Wang, Haifeng Chen, Jinyun Chen, Yue Sun, Weiwei Chen, Genhong Yao, Xiang Gao, Wanjun Chen, Songtao Shi, Xuebing Feng, Lingyun Sun
Patients with systemic lupus erythematosus (SLE) have a tremendously increased risk for cardiovascular disease (CVD), which could not be accounted in entirety by traditional Framingham risk factors. To study whether the accelerated atherosclerosis in SLE patients is mediated by type I interferon (IFN-I) through the regulation of endothelial progenitor cells (EPCs), we created a line of C57BL/6 mice with deficiency in both apolipoprotein E (ApoE-/-) and fas ligand (FasL-/-, gld.). As expected, the resultant gld...
September 2018: Current Research in Translational Medicine
Sang-Cheol Bae, Young Ho Lee
Our purpose was to identify differentially expressed (DE) genes and biological processes associated with gene expression changes in systemic lupus erythematosus (SLE). We performed a meta-analysis using the INMEX program (integrative meta-analysis of expression data) on publicly available microarray Genetic Expression Omnibus (GEO) datasets of peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We performed Gene Ontology (GO) enrichment analysis by using hypergeometric tests. In total, five comparisons (2 B cells, 2 CD4 T cells, and 1 myeloid cell) from two GEO datasets containing 51 cases and 46 controls were included in the meta-analysis...
July 30, 2018: Cellular and Molecular Biology
João J Oliveira, Sarah Karrar, Daniel B Rainbow, Christopher L Pinder, Pamela Clarke, Arcadio Rubio García, Osama Al-Assar, Keith Burling, Sian Morris, Richard Stratton, Tim J Vyse, Linda S Wicker, John A Todd, Ricardo C Ferreira
BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). METHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504)...
July 27, 2018: Arthritis Research & Therapy
Mrinal K Sarkar, Grace A Hile, Lam C Tsoi, Xianying Xing, Jianhua Liu, Yun Liang, Celine C Berthier, William R Swindell, Matthew T Patrick, Shuai Shao, Pei-Suen Tsou, Ranjitha Uppala, Maria A Beamer, Anshika Srivastava, Stephanie L Bielas, Paul W Harms, Spiro Getsios, James T Elder, John J Voorhees, Johann E Gudjonsson, J Michelle Kahlenberg
OBJECTIVE: Skin inflammation and photosensitivity are common in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), yet little is known about the mechanisms that regulate these traits. Here we investigate the role of interferon kappa (IFN-κ) in regulation of type I interferon (IFN) and photosensitive responses and examine its dysregulation in lupus skin. METHODS: mRNA expression of type I IFN genes was analysed from microarray data of CLE lesions and healthy control skin...
November 2018: Annals of the Rheumatic Diseases
Yasuhiro Kato, JeongHoon Park, Hyota Takamatsu, Hachirou Konaka, Wataru Aoki, Syunsuke Aburaya, Mitsuyoshi Ueda, Masayuki Nishide, Shohei Koyama, Yoshitomo Hayama, Yuhei Kinehara, Toru Hirano, Yoshihito Shima, Masashi Narazaki, Atsushi Kumanogoh
OBJECTIVE: Despite the importance of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) pathogenesis, the mechanisms of IFN-I production have not been fully elucidated. Recognition of nucleic acids by DNA sensors induces IFN-I and interferon-stimulated genes (ISGs), but the involvement of cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) and stimulator of interferon genes (STING) in SLE remains unclear. We studied the role of the cGAS-STING pathway in the IFN-I-producing cascade driven by SLE serum...
October 2018: Annals of the Rheumatic Diseases
Junlong Zhang, Xinle Liu, Yanming Meng, Hengxu Wu, Yongkang Wu, Bin Yang, Lanlan Wang
Systemic lupus erythematosus (SLE) has heterogeneous clinical manifestations. IFIH1 (interferon induced with helicase C domain 1) as one of antiviral helicase genes mediating type I interferon production, plays an essential role in the pathogenesis of SLE. The gene variants in IFIH1 could abnormally activate antiviral defenses and increased type I interferon signaling. The present study aimed to validate associations between single nucleotide polymorphisms (SNP) in IFIH1 and the pathogenesis of SLE. In total, rs1990760, rs3747517 and rs10930046 in IFIH1 are genotyped in 400 SLE patients and 659 health controls in Chinese cohort by an improved multiplex ligation detection reaction (iMLDR) technique...
June 21, 2018: Scientific Reports
Mindy S Lo
The pathophysiology of systemic lupus erythematosus (SLE) has been intensely studied but remains incompletely defined. Currently, multiple mechanisms are known to contribute to the development of SLE. These include inadequate clearance of apoptotic debris, aberrant presentation of self nucleic antigens, loss of tolerance, and inappropriate activation of T and B cells. Genetic, hormonal, and environmental influences are also known to play a role. The study of lupus in children, in whom there is presumed to be greater genetic influence, has led to new understandings that are applicable to SLE pathophysiology as a whole...
2018: Frontiers in Immunology
Gudny Ella Thorlacius, Marie Wahren-Herlenius, Lars Rönnblom
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share several clinical and laboratory features, including an overexpression of type I interferon (IFN) regulated genes. The genetic background to this IFN signature and the role of the type I IFN system in the disease process have been partly clarified. Here, we summarize the latest information concerning the type I IFN system in both diseases. RECENT FINDINGS: A number of gene variants in the type I IFN signalling pathways associate with an increased risk for both SLE and pSS in several ethnicities...
September 2018: Current Opinion in Rheumatology
Yudong Liu, Mariana J Kaplan
PURPOSE OF REVIEW: The mechanisms leading to the development of premature atherosclerosis and vascular injury in systemic lupus erythematosus (SLE) remain to be fully elucidated. This is a comprehensive review of recent research developments related to the understanding of cardiovascular disease (CVD) in lupus. RECENT FINDINGS: SLE patients with lupus nephritis display significantly increased risk of myocardial infarction and CVD mortality than SLE patients without lupus nephritis...
September 2018: Current Opinion in Rheumatology
Justine Calise, Susana Marquez Renteria, Peter K Gregersen, Betty Diamond
Interferon regulatory factor 5 (IRF5) is widely recognized as a risk locus for systemic lupus erythematosus (SLE). Risk gene and IRF5 activation is triggered through toll-like receptor signaling. In myeloid cells, this leads to production of type I interferon and inflammatory cytokines, with enhanced production in cells of individuals harboring IRF5 risk alleles. Mouse models have also demonstrated the importance of IRF5 in B cell function, particularly plasma cell differentiation and isotype switching. Here, we evaluated the major SLE risk haplotype of IRF5 on the functional attributes of freshly isolated B cells from human subjects who do not have evidence of SLE or other forms of autoimmunity...
2018: Frontiers in Immunology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"