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https://www.readbyqxmd.com/read/28818832/b-cell-ox40l-supports-t-follicular-helper-cell-development-and-contributes-to-sle-pathogenesis
#1
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunningham Grahman, Marina Botto, Timothy James Vyse
OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity...
August 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28814605/adam10-mediated-icos-ligand-shedding-on-b-cells-is-necessary-for-proper-t-cell-icos-regulation-and-t-follicular-helper-responses
#2
Joseph C Lownik, Andrea J Luker, Sheela R Damle, Lauren Folgosa Cooley, Riham El Sayed, Andreas Hutloff, Costantino Pitzalis, Rebecca K Martin, Mohey Eldin M El Shikh, Daniel H Conrad
The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for maintaining proper immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that a disintegrin and metalloproteinase (ADAM)10 is the primary physiological sheddase of ICOSL in mice and humans. Using an in vivo system in which ADAM10 is deleted only on B cells, elevated levels of ICOSL were seen...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807995/regulation-of-the-cell-cycle-and-inflammatory-arthritis-by-the-transcription-cofactor-lbh-gene
#3
Shinji Matsuda, Deepa Hammaker, Katharyn Topolewski, Karoline J Briegel, David L Boyle, Steven Dowdy, Wei Wang, Gary S Firestein
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28803918/modeling-of-trex1-dependent-autoimmune-disease-using-human-stem-cells-highlights-l1-accumulation-as-a-source-of-neuroinflammation
#4
Charles A Thomas, Leon Tejwani, Cleber A Trujillo, Priscilla D Negraes, Roberto H Herai, Pinar Mesci, Angela Macia, Yanick J Crow, Alysson R Muotri
Three-prime repair exonuclease 1 (TREX1) is an anti-viral enzyme that cleaves nucleic acids in the cytosol, preventing accumulation and a subsequent type I interferon-associated inflammatory response. Autoimmune diseases, including Aicardi-Goutières syndrome (AGS) and systemic lupus erythematosus, can arise when TREX1 function is compromised. AGS is a neuroinflammatory disorder with severe and persistent intellectual and physical problems. Here we generated a human AGS model that recapitulates disease-relevant phenotypes using pluripotent stem cells lacking TREX1...
August 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28799796/immune-modulation-by-curcumin-the-role-of-interleukin-10
#5
Hamid Mollazadeh, Arrigo F G Cicero, Christopher N Blesso, Matteo Pirro, Muhammed Majeed, Amirhossein Sahebkar
Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8(+) T cells, and TH1, TH2, and TH17 and regulatory T cells...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28795655/the-use-of-heart-rate-turbulence-and-heart-rate-variability-in-the-assessment-of-autonomic-regulation-and-circadian-rhythm-in-patients-with-systemic-lupus-erythematosus-without-apparent-heart-disease
#6
A R Poliwczak, E Waszczykowska, B Dziankowska-Bartkowiak, M Koziróg, K Dworniak
Background Systemic lupus erythematosus is a progressive autoimmune disease. There are reports suggesting that patients even without overt signs of cardiovascular complications have impaired autonomic function. The aim of this study was to assess autonomic function using heart rate turbulence and heart rate variability parameters indicated in 24-hour ECG Holter monitoring. Methods Twenty-six women with systemic lupus erythematosus and 30 healthy women were included. Twenty-four hour ambulatory ECG-Holter was performed in home conditions...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28795654/association-between-circulating-leptin-levels-and-systemic-lupus-erythematosus-an-updated-meta-analysis
#7
Y H Lee, G G Song
Objective We aimed to evaluate the relationship between circulating leptin levels and systemic lupus erythematosus (SLE). Methods MEDLINE, EMBASE, and Cochrane library databases were searched. Meta-analyses were performed comparing serum/plasma leptin levels in patients with SLE and healthy controls, and on patients with SLE in subgroups based on ethnicity, sample size, data type, and matched variables (age, sex, and/or body mass index (BMI)). Results Eighteen studies including 1333 patients with SLE and 1048 controls were ultimately selected, which showed that leptin levels were significantly higher in the SLE group than in the control group (SMD = 0...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28791351/altered-gene-expression-profile-in-a-rat-model-of-gentamicin-induced-ototoxicity-and-nephrotoxicity-and-the-potential-role-of-upregulated-ifi44-expression
#8
Jun-Gen Hu, Yu Fu, Jian-Ju Xu, Xian-Ping Ding, Hui-Qi Xie, Jesse Li-Ling
As demonstrated by Alport syndrome, the co‑occurrence of auditory and urinary system malformations, and gentamicin-induced ototoxicity and nephrotoxicity, the ears and kidneys potentially share certain molecular pathways. In the present study, microarray chips were used to analyze the changes in the gene expression profile using a rat model of gentamicin‑induced ototoxicity and nephrotoxicity, using rat liver tissue as a control. A number of genes were identified to exhibit similar expression changes in the rat ears and kidney tissues, among which microtubule‑associated protein 44 (Ifi44), was selected for further analysis to validate its expression changes and confirm potential involvement in the inflammation process in the disease model...
August 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28781371/t-helper-type-17-cells-in-immune-mediated-glomerular-disease
#9
REVIEW
Christian F Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer
CD4(+) T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4(+) T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6)...
August 7, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28774715/dendritic-cell-recruitment-and-activation-in-autoimmunity
#10
REVIEW
Silvano Sozzani, Annalisa Del Prete, Daniela Bosisio
Dendritic cells (DCs) are professional antigen presenting cells displaying the unique capability to activate naïve T cells. DCs react to pathogen encounter also by the production of mediators of inflammation, including pro-inflammatory cytokines. Because of this complex role, any imbalance in DC function reflects into defective or exaggerated immune response and tissue damage. DCs comprise two main subsets, namely conventional or classical DCs (cDCs), that are dedicated antigen presenting cells, and plasmacytoid DCs (pDCs), that respond to nucleic acids by releasing high amounts of type I interferons (IFNs)...
July 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#11
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28755900/assessment-of-urinary-tweak-levels-in-mexican-patients-with-untreated-lupus-nephritis-an-exploratory-study
#12
Fabiola Reyes-Martínez, Monserrat Pérez-Navarro, Adrián Rodríguez-Matías, Virgilia Soto-Abraham, Gabriela Gutierrez-Reyes, Zaira Medina-Avila, Rafael Valdez-Ortiz
OBJECTIVES: Urinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. METHODS: An exploratory study was performed; four groups of patients were analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3) patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and healthy patients (controls)...
July 26, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28755727/plasma-antiphospholipid-antibodies-effects-on-activated-partial-thromboplastin-time-assays
#13
Ke Yao, Lingyun Zhang, Hang Zhou, Ning Tang, Dengju Li
BACKGROUND: Activated partial thromboplastin time (aPTT) assays can be affected by plasma antiphospholipid antibodies (aPLs), but the degree of the interference is not easy to predict. This study aimed to investigate the effects on aPTT assay results of different types and combinations of aPLs, including anti-β2-glycoprotein I antibodies, anticardiolipin antibodies and lupus anticoagulant. MATERIALS AND METHODS: We retrospectively collected clinical information and laboratory tests from aPL-positive patients...
July 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#14
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28745692/-changes-in-the-complement-system-in-membranoproliferative-glomerulonephritis
#15
V A Yurova, L A Bobrova, N L Kozlovskaya, Yu V Korotchaeva, A G Serova, L V Kozlov, S S Andina, K A Demyanova, A M Kuchieva, S V Roshchupkina
AIM: To compare the clinical manifestations membranoproliferative glomerulonephritis (MPGN) in its idiopathic variant, lupus nephritis (LN), and C3 glomerulopathy (C3-GP), by comparing them with changes in the complement system. SUBJECTS AND METHODS: The clinic of nephrology followed up 42 patients with different types of MPGN in 2013 to 2015. The study included 35 patients divided into 3 groups: 1) 8 patients with C3-GP, 2) 13 with idiopathic MPGN; 3) 14 with Class IV LN...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28745510/statistical-models-for-the-analysis-of-isobaric-tags-multiplexed-quantitative-proteomics
#16
Gina D'Angelo, Raghothama Chaerkady, Wen Yu, Deniz Baycin Hizal, Sonja Hess, Wei Zhao, Kristen Lekstrom, Xiang Guo, Wendy I White, Lorin Roskos, Michael A Bowen, Harry Yang
Mass spectrometry is being used to identify protein biomarkers that can facilitate development of drug treatment. Mass spectrometry-based labeling proteomic experiments result in complex proteomic data that is hierarchical in nature often with small sample size studies. The generalized linear model (GLM) is the most popular approach in proteomics to compare protein abundances between groups. However, GLM does not address all the complexities of proteomics data such as repeated measures and variance heterogeneity...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28736376/-protective-effects-of-glycyrrhizic-acid-against-lupus-nephritis-in-mrl-lpr-mice
#17
Yuan-Yuan Wang, Hong-Tao Li, Yang Lu, Xiao-Yun Jia, Yang-Lei Li, Sheng Chen, Ji-Xia Chai, Jia-Jia Zhang, Dong Liu, Chang-Hao Xie
OBJECTIVE: To investigate protective effect of glycyrrhizic acid (GA) against lupus nephritis in MRL/lpr mice and explore its underlying mechanisms. METHODS: Forty MRL/lpr mice were randomized equally into blank control group, dexamethasone (1.5 mg/kg) group, GA (20 mg/kg) group, and GA (40 mg/kg) group with corresponding treatments for 7 days, with 10 wild-type mice as the control group. Serum levels of uric acid and creatinine and inflammatory cytokines in the serum and kidney were tested after the treatments using enzyme-linked immunosorbent assays (ELISA)...
July 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28727732/incidence-of-thromboembolic-events-in-asymptomatic-carriers-of-iga-anti-%C3%A3-2-glycoprotein-i-antibodies
#18
Carlos Tortosa, Oscar Cabrera-Marante, Manuel Serrano, José A Martínez-Flores, Dolores Pérez, David Lora, Luis Morillas, Estela Paz-Artal, José M Morales, Daniel Pleguezuelo, Antonio Serrano
BACKGROUND: The antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined...
2017: PloS One
https://www.readbyqxmd.com/read/28722531/patterns-of-renal-disease-in-south-korea-a-20-year-review-of-a-single-center-renal-biopsy-database
#19
Ho Sik Shin, Dae Hyeon Cho, Soo Kyoung Kang, Hyun Jeong Kim, Soo Young Kim, Joung Wook Yang, Gyong Hoon Kang, Ye Na Kim, Yeonsoon Jung, Bong-Kwon Cheon, Hark Rim
BACKGROUND: Several registries and centers have reported the results of renal biopsies from different parts of the world. As there are few data regarding the epidemiology of glomerulonephritis (GN) in South Korea, we conducted this study on renal biopsy findings during the last 20 years from a single center. METHODS: Data for 818 patients who underwent renal biopsy at our center between 1992 and 2011 were collected retrospectively. All kidney specimens were examined with light microscopy (LM) and immunofluorescent microscopy (IF)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#20
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
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