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https://www.readbyqxmd.com/read/27906046/chromatin-landscapes-and-genetic-risk-in-systemic-lupus
#1
Joyce S Hui-Yuen, Lisha Zhu, Lai Ping Wong, Kaiyu Jiang, Yanmin Chen, Tao Liu, James N Jarvis
BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27904655/increased-set1-binding-at-the-promoter-induces-aberrant-epigenetic-alterations-and-up-regulates-cyclic-adenosine-5-monophosphate-response-element-modulator-alpha-in-systemic-lupus-erythematosus
#2
Qing Zhang, Shu Ding, Huilin Zhang, Hai Long, Haijing Wu, Ming Zhao, Vera Chan, Chak-Sing Lau, Qianjin Lu
BACKGROUND: Up-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE. RESULTS: From the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27903979/elevated-plasma-midkine-and-pleiotrophin-levels-in-patients-with-systemic-lupus-erythematosus
#3
Guo-Cui Wu, Hui Yuan, Hai-Feng Pan, Dong-Qing Ye
Emerging evidence suggests that two heparin-binding growth factor, midkine and pleiotrophin are implicated in the pathogenesis of autoimmune diseases including SLE. To investigate the plasma midkine and pleiotrophin levels in SLE patients, as well as their correlation with major clinical parameters and interleukin-17 (IL-17) level in SLE, 83 SLE patients and 123 controls including 20 rheumatoid arthritis (RA) patients, 21 Sjögren's syndrome (SS) patients and 82 healthy controls (HCs) were recruited. Plasma midkine, pleiotrophin and IL-17 levels were detected by ELISA...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902995/systemic-lupus-erythematosus-a-review-of-the-clinical-approach-to-diagnosis-and-update-on-current-targeted-therapies
#4
Joanne Szczygiel Cunha, Katarzyna Gilek-Seibert
Systemic lupus erythematosus (SLE) is a chronic, complicated and challenging disease to diagnose and treat. The etiology of SLE is unknown, but certain risk factors have been identified that lead to immune system dysfunction with antibody formation and immune complex deposition. This immune system dysregulation causes organ injury, contributing to the variable manifestations and relapsing-remitting course of the disease. Criteria were created to aide in the diagnosis, focusing on clinical manifestations and antibody profiles specific to SLE...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27885845/dna-methylation-in-systemic-lupus-erythematosus
#5
Christian M Hedrich, Katrin Mäbert, Thomas Rauen, George C Tsokos
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease facilitated by aberrant immune responses directed against cells and tissues, resulting in inflammation and organ damage. In the majority of patients, genetic predisposition is accompanied by additional factors conferring disease expression. While the exact molecular mechanisms remain elusive, epigenetic alterations in immune cells have been demonstrated to play a key role in disease pathogenesis through the dysregulation of gene expression...
November 25, 2016: Epigenomics
https://www.readbyqxmd.com/read/27884379/purinergic-signalling-in-autoimmunity-a-role-for-the-p2x7r-in-systemic-lupus-erythematosus
#6
REVIEW
Francesco Di Virgilio, Anna Lisa Giuliani
Purinergic signalling plays a crucial role in immunity and autoimmunity. Among purinergic receptors, the P2X7 receptor (P2X7R) has an undisputed role as it is expressed to high level by immune cells, triggers cytokine release and modulates immune cell differentiation. In this review, we focus on evidence supporting a possible role of the P2X7R in the pathogenesis of systemic lupus erythematosus (SLE).
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27884376/purinergic-signaling-in-infection-and-autoimmune-disease
#7
EDITORIAL
Luiz Eduardo Baggio Savio, Robson Coutinho-Silva
Purinergic signaling plays a key role in inflammatory processes and modulates immune responses against a variety of bacterial and eukaryotic parasites. Here we highlight the role of purinergic receptor activation in infection and autoimmune diseases. Purinergic signaling and inflammasomes modulate the host immune response against chlamydial infections. In addition, increasing evidence suggests that purinergic signaling contributes to Schistosomiasis morbidity, a neglected tropical disease caused by parasitic worms called schistosomes...
October 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27882473/foxp3-regulatory-t-cell-and-autoimmune-diseases
#8
REVIEW
Jin-Hui Tao, Miao Cheng, Jiang-Ping Tang, Qin Liu, Fan Pan, Xiang-Pei Li
Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#9
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27878683/april-gene-polymorphism-and-serum-sapril-levels-in-children-with-systemic-lupus-erythematosus
#10
Shideh Namazi, Nader Tajik, Vahid Ziaee, Maryam Sadr, Samaneh Soltani, Arezou Rezaei, Samaneh Zoghi, Nima Rezaei
Systemic lupus erythematosus (SLE) is a multi-factor autoimmune disorder with diverse clinical manifestations and unclear pathogenesis. Genetic components play important roles in the incidence and development of SLE. Among these, APRIL as a cytokine has roles in the stimulation and antibody production in B cells. APRIL was hypothesized to be associated with SLE. The aim of this study was to assess the involvement of the APRIL gene in SLE susceptibility in Iranian patients. A single-nucleotide polymorphism (SNP) for rs11552708 of APRIL gene was analyzed by real-time PCR in 60 SLE Iranian children and 64 healthy controls...
November 23, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27872476/new-insights-into-the-immunopathogenesis-of-systemic-lupus-erythematosus
#11
REVIEW
George C Tsokos, Mindy S Lo, Patricia Costa Reis, Kathleen E Sullivan
The aetiology of systemic lupus erythematosus (SLE) is multifactorial, and includes contributions from the environment, stochastic factors, and genetic susceptibility. Great gains have been made in understanding SLE through the use of genetic variant identification, mouse models, gene expression studies, and epigenetic analyses. Collectively, these studies support the concept that defective clearance of immune complexes and biological waste (such as apoptotic cells), neutrophil extracellular traps, nucleic acid sensing, lymphocyte signalling, and interferon production pathways are all central to loss of tolerance and tissue damage...
November 22, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27867381/a-critical-reappraisal-of-neutrophil-extracellular-traps-and-netosis-mimics-based-on-differential-requirements-for-protein-citrullination
#12
Maximilian F Konig, Felipe Andrade
NETosis, an antimicrobial form of neutrophil cell death, is considered a primary source of citrullinated autoantigens in rheumatoid arthritis (RA) and immunogenic DNA in systemic lupus erythematosus (SLE). Activation of the citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is believed to be essential for neutrophil extracellular trap (NET) formation and NETosis. PAD4 is therefore viewed as a promising therapeutic target to inhibit the formation of NETs in both diseases. In this review, we examine the evidence for PAD4 activation during NETosis and provide experimental data to suggest that protein citrullination is not a universal feature of NETs...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27863504/b-cell-imaging-with-zirconium-89-labelled-rituximab-pet-ct-at-baseline-is-associated-with-therapeutic-response-24%C3%A2-weeks-after-initiation-of-rituximab-treatment-in-rheumatoid-arthritis-patients
#13
Stefan Bruijnen, Michel Tsang-A-Sjoe, Hennie Raterman, Tamara Ramwadhdoebe, Daniëlle Vugts, Guus van Dongen, Marc Huisman, Otto Hoekstra, Paul-Peter Tak, Alexandre Voskuyl, Conny van der Laken
BACKGROUND: B cells are key players in the pathogenesis of rheumatoid arthritis (RA). Although successful in 50-60% of patients with RA, anti-B-cell therapy given as rituximab could be more efficient by identifying potential responders prior to treatment. Positron emission tomography (PET) using radiolabeled rituximab for B-cell imaging might provide the means to fulfil this unmet clinical need. The objective of this study was to investigate the association between biodistribution of zirconium-89 ((89)Zr)-rituximab on PET-computed tomography (CT) and clinical response in patients with RA...
November 18, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27863149/cgas-expression-in-patients-with-systemic-lupus-erythematosus
#14
Jie An, Laura Durcan, Reynold M Karr, Tracy A Briggs, Gillian I Rice, Thomas H Teal, Joshua J Woodward, Keith B Elkon
OBJECTIVES Type I interferon (IFN-I) is implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) and 'interferonopathies' such as Aicardi-Goutieres Syndrome. A recently discovered DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS) is linked to AGS and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to IFN-I production in SLE patients. METHODS SLE disease activity was measured by SELENA-SLEDAI. cGAS and interferon stimulated gene (ISG) mRNA expression was quantified by quantitative PCR ...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27852746/human-basophils-modulate-plasma-cell-differentiation-and-maturation
#15
Dorothea Dijkstra, Almut Meyer-Bahlburg
Basophils represent <1% of circulating leukocytes. They play a crucial role during allergy and helminth-induced Th2 responses. However, recent data also suggest a contribution to the pathogenesis of autoimmune diseases. Basophils from patients with systemic lupus erythematosus show an activated phenotype, correlating to disease activity. Furthermore, murine basophils or their mediators enhance memory responses and plasma cell (PC) survival, suggesting that they directly modulate the function of B cells. This is highly relevant with respect to human allergy and autoimmunity because a possible modulation of B cell differentiation by basophils could point to new therapeutic targets...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27852285/elevated-expression-of-mir-142-3p-is-related-to-the-pro-inflammatory-function-of-monocyte-derived-dendritic-cells-in-sle
#16
Yilun Wang, Jun Liang, Haihong Qin, Yan Ge, Juan Du, Jinran Lin, Xiaohua Zhu, Jie Wang, Jinhua Xu
BACKGROUND: Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of the alteration remains unclear. METHODS: We cultured monocyte-derived DCs (moDCs) in vitro and examined the cytokines and chemokines in the supernatants of moDCs in negative controls (NC) and SLE patients in active phase. We then profiled microRNAs (miRNAs) of LPS-stimulated moDCs in SLE patients and used real-time PCR to verify the differentially expressed miRNAs...
November 16, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27847409/effect-of-interleukin-15-on-cd11b-cd54-and-cd62l-expression-on-natural-killer-cell-and-natural-killer-t-like-cells-in-systemic-lupus-erythematosus
#17
Syh-Jae Lin, Ji-Yih Chen, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Jing-Long Huang
Adhesion molecules may play an important role in systemic lupus erythematosus (SLE) pathogenesis. We investigated the effect of interleukin- (IL-) 15 on CD11b, CD54, and CD62L expression on natural killer (NK) cells, T cells, and CD56(+)CD3(+) NKT-like cells from SLE subjects and healthy controls. SLE patients had decreased circulating NK cells and NKT-like cells compared to controls. NK cells from SLE patients showed higher CD11b and CD62L expression compared to controls. IL-15 enhanced CD11b and CD54 but downregulated CD62L expression on NK cells from SLE patients...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27837104/cutting-edge-baff-overexpression-reduces-atherosclerosis-via-taci-dependent-b-cell-activation
#18
Shaun W Jackson, Nicole E Scharping, Holly M Jacobs, Shari Wang, Alan Chait, David J Rawlings
Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis...
November 11, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27836780/oxidative-stress-leads-to-reduction-of-plasmalogen-serving-as-a-novel-biomarker-for-systemic-lupus-erythematosus
#19
Changfeng Hu, Jia Zhou, Shasha Yang, Haichang Li, Chunyan Wang, Xiaoling Fang, Yongsheng Fan, Jida Zhang, Xianlin Han, Chengping Wen
Oxidative stress is elevated in systemic lupus erythematosus (SLE) patients, and associated extensively with SLE pathogenesis. However, no common indicators of oxidative stress are yet in routine clinical use because of their instability, nonspecificity, and non-representation of all SLE symptoms. Moreover, the method for reproducible analysis of reactive oxygen species is still lacking. Lipids and their metabolites are essential components of biological systems, many of which serve as molecular targets of oxidative stress and play crucial roles in signaling, inflammation, and immune responses...
November 9, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27828627/inflammasomes-and-dermatology
#20
Daniel Coelho de Sá, Cyro Festa
Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA)...
September 2016: Anais Brasileiros de Dermatologia
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