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interferon type I AND SLE

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https://www.readbyqxmd.com/read/30084812/meta-analysis-of-gene-expression-profiles-of-peripheral-blood-cells-in-systemic-lupus-erythematosus
#1
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
https://www.readbyqxmd.com/read/30053827/the-plasma-biomarker-soluble-siglec-1-is-associated-with-the-type-i-interferon-transcriptional-signature-ethnic-background-and-renal-disease-in-systemic-lupus-erythematosus
#2
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
https://www.readbyqxmd.com/read/30021804/photosensitivity-and-type-i-ifn-responses-in-cutaneous-lupus-are-driven-by-epidermal-derived-interferon-kappa
#3
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...
July 18, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29945921/apoptosis-derived-membrane-vesicles-drive-the-cgas-sting-pathway-and-enhance-type-i-ifn-production-in-systemic-lupus-erythematosus
#4
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...
June 26, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29930297/autoimmune-disease-associated-ifih1-single-nucleotide-polymorphism-related-with-il-18-serum-levels-in-chinese-systemic-lupus-erythematosus-patients
#5
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
https://www.readbyqxmd.com/read/29922296/insights-gained-from-the-study-of-pediatric-systemic-lupus-erythematosus
#6
REVIEW
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
https://www.readbyqxmd.com/read/29889694/an-update-on-the-role-of-type-i-interferons-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome
#7
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
https://www.readbyqxmd.com/read/29870498/cardiovascular-disease-in-systemic-lupus-erythematosus-an-update
#8
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
https://www.readbyqxmd.com/read/29867973/lineage-specific-functionality-of-an-interferon-regulatory-factor-5-lupus-risk-haplotype-lack-of-b-cell-intrinsic-effects
#9
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
https://www.readbyqxmd.com/read/29860420/regulation-and-role-of-the-transcription-factor-irf5-in-innate-immune-responses-and-systemic-lupus-erythematosus
#10
Tatsuma Ban, Go R Sato, Tomohiko Tamura
The transcription factor interferon regulatory factor-5 (IRF5) plays an important role in innate immune responses via the TLR-MyD88 (Toll-like receptor - myeloid differentiation primary response 88) pathway. IRF5 is also involved in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Recent studies have identified new regulators, both positive and negative, which act on IRF5 activation events in the TLR-MyD88 pathway such as post-translational modifications, dimerization and nuclear translocation...
May 31, 2018: International Immunology
https://www.readbyqxmd.com/read/29850618/conventional-dcs-from-male-and-female-lupus-prone-b6-nzm-sle1-sle2-sle3-mice-express-an-ifn-signature-and-have-a-higher-immunometabolism-that-are-enhanced-by-estrogen
#11
Michael H Lee, Marita Chakhtoura, Uma Sriram, Roberto Caricchio, Stefania Gallucci
Type I interferons (IFN) are pathogenic in systemic lupus erythematosus (SLE) and were proposed to control the immunometabolism of dendritic cells (DCs). We previously reported that DCs from female lupus-prone mice constitutively overexpress IFN-responsive genes resembling the IFN signature found in SLE patients. As SLE has higher incidence in women than men, more so in women of reproductive age, estrogens are suggested to affect lupus pathogenesis. We investigated the effects of sex and estrogens on the IFN signature in conventional GM-CSF-bone marrow-derived DCs (cDCs), from male and female Triple Congenic B6...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29807382/-systemic-lupus-erythematosus-sle-new-classification-criteria
#12
Martin Aringer, Thomas Dörner
The work on new classification criteria for SLE supported by both EULAR and ACR has led to the reconfirmation that almost all SLE patients are ANA positive. The criteria developed now rely on ANA as an entry criterion and weighted additive criteria. Remission criteria have reached international consensus, which combine the absence of inflammatory activity with glucocorticoids of not higher than 5 mg prednisolone/prednisone q. d. This is also meant to reduce the excessive risk of atherosclerosis, where ASS and moderate alcohol consumption appear to be helpful...
June 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29806091/elevated-ifit3-contributes-to-abnormal-overactive-cgas-sting-signaling-in-human-systemic-lupus-erythematosus-monocytes
#13
Jiehua Wang, Min Dai, Yange Cui, Guojun Hou, Jun Deng, Xin Gao, Zhuojun Liao, Ya Liu, Yao Meng, Lingling Wu, Chao Yao, Yan Wang, Jie Qian, Qiang Guo, Huihua Ding, Bo Qu, Nan Shen
OBJECTIVE: Increasing evidence indicate a critical pathogenic role of cGAS-STING signaling pathway in systemic lupus erythematosus (SLE). Interferon(IFN) inducible gene, IFIT3, is elevated in SLE. However, it is still not clear how IFIT3 contributes to SLE pathogenesis. We undertook this study to investigate the activation of cGAS-STING signaling pathway in SLE monocytes, as well as how elevated IFIT3 contributes to the overactivation of cGAS-STING signaling pathway. METHODS: Monocytes from SLE patients or healthy controls were examined for the activity of cGAS-STING signaling pathway and expression of IFIT3...
May 27, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29781188/a-novel-anti-malarial-drug-derivative-inhibits-cyclic-gmp-amp-synthase-in-trex1-deficient-mice
#14
Jie An, Joshua J Woodward, Weinan Lai, Mark Minie, Xizhang Sun, Lena Tanaka, Jessica M Snyder, Tomikazu Sasaki, Keith B Elkon
OBJECTIVE: Type I interferon (IFN-I) is strongly implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) as well as rare monogenic 'interferonopathies' such as Aicardi-Goutieres Syndrome (AGS) caused by mutations in the DNA exonuclease, TREX1. The DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS), is linked to subsets of AGS and lupus. We identified inhibitors of DNA-cGAS interaction and tested lead candidate, X6, in a mouse model of AGS. METHODS: Trex1-/- mice were treated orally from birth with either X6 or HCQ for 8 weeks...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29774490/higher-activation-of-the-interferon-gamma-signaling-pathway-in-systemic-lupus-erythematosus-patients-with-a-high-type-i-ifn-score-relation-to-disease-activity
#15
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29766256/monogenic-systemic-lupus-erythematosus-insights-in-pathophysiology
#16
REVIEW
Ezgi Deniz Batu
Systemic lupus erythematosus (SLE) is a complex disease with different genetic, immunologic, and environmental factors contributing to the pathogenesis. Monogenic SLE could help us understand the main phases of immune dysregulation in SLE. The aim of this review is to summarize the current knowledge on monogenic SLE with the implications of the respective genes on disease pathogenesis. A comprehensive literature search on monogenic SLE was conducted utilizing the Cochrane Library and MEDLINE/PubMed databases...
May 15, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29673738/tbk1-a-key-regulator-and-potential-treatment-target-for-interferon-positive-sj%C3%A3-gren-s-syndrome-systemic-lupus-erythematosus-and-systemic-sclerosis
#17
Iris L A Bodewes, Erika Huijser, Cornelia G van Helden-Meeuwsen, Liselotte Tas, Ruth Huizinga, Virgil A S H Dalm, P Martin van Hagen, Noortje Groot, Sylvia Kamphuis, Paul L A van Daele, Marjan A Versnel
OBJECTIVE: Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs)...
July 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29644082/characterisation-of-anifrolumab-a-fully-human-anti-interferon-receptor-antagonist-antibody-for-the-treatment-of-systemic-lupus-erythematosus
#18
Jeffrey M Riggs, Richard N Hanna, Bhargavi Rajan, Kamelia Zerrouki, Jodi L Karnell, Divya Sagar, Inna Vainshtein, Erika Farmer, Kimberly Rosenthal, Chris Morehouse, Melissa de Los Reyes, Kevin Schifferli, Meina Liang, Miguel A Sanjuan, Gary P Sims, Roland Kolbeck
Objective: We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods: IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element-luciferase reporter cell assays and type I IFN gene signature induction...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29644080/safety-tolerability-and-pharmacokinetics-of-subcutaneous-and-intravenous-anifrolumab-in-healthy-volunteers
#19
Raj Tummala, Tomas Rouse, Anna Berglind, Linda Santiago
Objectives: To compare the pharmacokinetics (PK), safety and tolerability of subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon receptor monoclonal antibody in development for SLE, in healthy volunteers. Methods: In this Phase I randomised, placebo-controlled study, 30 adults were assigned to three treatment cohorts (anifrolumab 300 mg SC (n=6), anifrolumab 300 mg intravenous (n=6), anifrolumab 600 mg SC (n=6)) and placebo (n=4/cohort)...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29643425/a-novel-two-score-system-for-interferon-status-segregates-autoimmune-diseases-and-correlates-with-clinical-features
#20
Y M El-Sherbiny, A Psarras, M Y Md Yusof, E M A Hensor, R Tooze, G Doody, A A A Mohamed, D McGonagle, M Wittmann, P Emery, E M Vital
Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls...
April 11, 2018: Scientific Reports
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