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https://www.readbyqxmd.com/read/30315781/enhancer-connectome-nominates-target-genes-of-inherited-risk-variants-from-inflammatory-skin-disorders
#1
Mark Y Jeng, Maxwell R Mumbach, Jeffrey M Granja, Ansuman T Satpathy, Howard Y Chang, Anne Lynn S Chang
The vast majority of polymorphisms for human dermatologic diseases fall in non-coding DNA regions, leading to difficulty interpreting their functional significance. Recent work utilizing chromosome conformation capture (3C) technology in combination with chromatin immunoprecipitation (ChIP) has provided a systematic means of linking non-coding variants within active enhancer loci to putative gene targets. Here, we apply H3K27ac HiChIP high-resolution contact maps, generated from primary human T-cell subsets (CD4+ Naïve, TH 17, and Treg ), to 21 dermatologic conditions associated with single nucleotide polymorphisms (SNPs) from 106 genome-wide association studies (GWAS)...
October 10, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30314758/distinct-effector-b-cells-induced-by-unregulated-toll-like-receptor-7-contribute-to-pathogenic-responses-in-systemic-lupus-erythematosus
#2
Scott A Jenks, Kevin S Cashman, Esther Zumaquero, Urko M Marigorta, Aakash V Patel, Xiaoqian Wang, Deepak Tomar, Matthew C Woodruff, Zoe Simon, Regina Bugrovsky, Emily L Blalock, Christopher D Scharer, Christopher M Tipton, Chungwen Wei, S Sam Lim, Michelle Petri, Timothy B Niewold, Jennifer H Anolik, Greg Gibson, F Eun-Hyung Lee, Jeremy M Boss, Frances E Lund, Ignacio Sanz
Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5- CD11c+ cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased Toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7...
October 3, 2018: Immunity
https://www.readbyqxmd.com/read/30308137/association-of-soluble-trem-like-transcript-1-with-clinical-features-and-patient-reported-outcomes-in-systemic-lupus-erythematosus
#3
Ileana Vázquez-Otero, Yerania Rodríguez-Navedo, Karina Vilá-Rivera, Mariely Nieves-Plaza, Jessica Morales-Ortiz, A Valance Washington, Luis M Vilá
OBJECTIVE: The soluble triggering receptor expressed on myeloid cells (TREM-1)-like transcript 1 (sTLT1) has a modulatory effect on the activation of TREM-1. We compared plasma sTLT-1 levels between patients with systemic lupus erythematosus (SLE) and healthy individuals and determined the association between sTLT-1 levels and clinical features and patient-reported outcomes (PROs) among patients with lupus. METHODS: An unmatched case-control study was conducted in 46 patients with SLE and 28 healthy subjects...
October 10, 2018: European Journal of Rheumatology
https://www.readbyqxmd.com/read/30305312/curli-containing-enteric-biofilms-inside-and-out-matrix-composition-immune-recognition-and-disease-implications
#4
REVIEW
Sarah A Tursi, Çagla Tükel
Biofilms of enteric bacteria are highly complex, with multiple components that interact to fortify the biofilm matrix. Within biofilms of enteric bacteria such as Escherichia coli and Salmonella species, the main component of the biofilm is amyloid curli. Other constituents include cellulose, extracellular DNA, O antigen, and various surface proteins, including BapA. Only recently, the roles of these components in the formation of the enteric biofilm individually and in consortium have been evaluated. In addition to enhancing the stability and strength of the matrix, the components of the enteric biofilm influence bacterial virulence and transmission...
December 2018: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/30301670/right-ventricular-function-is-associated-with-quality-of-life-in-patients-with-systemic-lupus-erythematosus-associated-pulmonary-arterial-hypertension
#5
Hui Wang, Qian Wang, Zhuang Tian, Xiaoxiao Guo, Jinzhi Lai, Mengtao Li, Jiuliang Zhao, Yongtai Liu, Xiaofeng Zeng, Quan Fang
BACKGROUND: Right ventricular (RV) function has been identified as an important determinant of outcome in patients with pulmonary hypertension. We aimed to investigate the relationship between echocardiographic-derived RV function and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus associated pulmonary arterial hypertension (SLE-APAH), and to identify the best echocardiographic parameter for evaluating RV function in these patients. METHODS: Sixty consecutive patients with SLE-APAH (all female, mean age 33...
September 27, 2018: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/30301579/epigenome-wide-association-study-of-peripheral-blood-mononuclear-cells-in-systemic-lupus-erythematosus-identifying-dna-methylation-signatures-associated-with-interferon-related-genes-based-on-ethnicity-and-sledai
#6
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
https://www.readbyqxmd.com/read/30301440/gata3-rs3824662-gene-polymorphism-as-possible-risk-factor-for-systemic-lupus-erythematosus
#7
Y M Mosaad, A Hammad, A A Elghzaly, Z M E Tawhid, E M Hammad, A Showma, R Abdelsalam, A Elmoughy, I M Fawzy, N Anber
Background There is no report about the association between GATA3 rs3824662 polymorphism and systemic lupus erythematosus (SLE). Objective To investigate the possible role of GATA3 rs3824662 polymorphism as a susceptibility risk factor for either adult SLE (aSLE) or pediatric SLE (pSLE) and to evaluate its role in the development of lupus nephritis (LN) in pSLE. Methods Typing of GATA3 rs3824662 polymorphism was done using real-time polymerase chain reaction for three groups; 104 pSLE patients, 140 aSLE patients and 436 age- and sex-matched healthy controls...
October 9, 2018: Lupus
https://www.readbyqxmd.com/read/30301439/urinary-b-cell-activating-factor-of-the-tumour-necrosis-factor-family-baff-in-systemic-lupus-erythematosus
#8
F B Vincent, R Kandane-Rathnayake, A Y Hoi, L Slavin, J D Godsell, A R Kitching, J Harris, C L Nelson, A J Jenkins, A Chrysostomou, M L Hibbs, P G Kerr, M Rischmueller, F Mackay, E F Morand
Introduction We examined the clinical relevance of urinary concentrations of B-cell-activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). Methods We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified...
October 9, 2018: Lupus
https://www.readbyqxmd.com/read/30298658/lupus-nephritis-an-update-on-treatments-and-pathogenesis
#9
REVIEW
Desmond Yh Yap, Susan Yung, Tak Mao Chan
Immunosuppressive therapies for lupus nephritis (LN) have improved significantly over the past few decades, resulting in growing number of choices for treatment individualization and improved renal and patient outcomes. Corticosteroids combined with mycophenolate or cyclophosphamide induces a satisfactory response in a high proportion of Asian and Caucasian patients, but the rate of improvement varies considerably between patients. Relatively low disease flare rate was observed in Chinese patients receiving low-dose prednisolone and mycophenolate maintenance...
October 2018: Nephrology
https://www.readbyqxmd.com/read/30298653/complement-in-glomerular-diseases
#10
REVIEW
Ying Tan, Ming-Hui Zhao
Complement activation has been identified to play a vital role in the pathogenesis of many glomerulonephritis, either as direct complement activation-driven factor in thrombotic microangiopathy and C3 glomerulopathy, and/or as an important contributor in lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis. Recent studies indicated that complement activation may also play roles in the pathogenesis of immunoglobulin A nephropathy and focal segmental glomerulosclerosis. Interestingly, monoclonal immunoglobulins/light chains from patients with monoclonal gammopathy may interfere with complement activation and thus indirectly result in complement-mediated glomerulonephritis...
October 2018: Nephrology
https://www.readbyqxmd.com/read/30297159/arid3a-gene-profiles-are-strongly-associated-with-human-interferon-alpha-production
#11
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
https://www.readbyqxmd.com/read/30296972/imaging-of-joints-in-systemic-lupus-erythematosus
#12
REVIEW
Chiara Tani, Linda Carli, Chiara Stagnaro, Elena Elefante, Viola Signorini, Francesca Balestri, Andrea Delle Sedie, Marta Mosca
Musculoskeletal symptoms are among the most common manifestations in patients with systemic lupus erythematosus (SLE), being reported in up to 95% of patients; joint and tendon involvement can range from arthralgia to severe deforming arthropathy; while myositis a rare manifestation, comorbid fibromyalgia is reported in up to 40% of SLE patients. All these manifestations have a significant impact on the patients' quality of life, possibly leading to disability and functional impairment in daily living activities...
September 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/30294950/blood-concentrations-of-complement-split-product-ic3b-and-serum-c3-associate-with-sle-disease-activity
#13
Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson
OBJECTIVE: To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE). METHODS: 159 consecutive subjects with American College of Rheumatology or Systemic Lupus International Collaborating Clinics classified SLE were enrolled into CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study...
October 8, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/30292636/mtor-inhibitor-ink128-attenuates-systemic-lupus-erythematosus-by-regulating-inflammation-induced-cd11b-gr1-cells
#14
Guoping Shi, Dan Li, Xiaojing Li, Jing Ren, Jingjing Xu, Liang Ding, Huan Dou, Yayi Hou
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by systemic chronic inflammation that can affect multiple major organ systems. Although the etiology of SLE is known to involve a variety of factors such as the environment, random factors and genetic susceptibility, the exact role of inflammation induced CD11b+ Gr1+ myeloid cells in the early stage of lupus progression is not fully understood. Myeloid-derived CD11b+ Gr1+ cells are thought to be a heterogeneous group of immature myeloid cells with immune function...
October 4, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30290988/discovery-of-a-novel-series-of-pyridine-and-pyrimidine-carboxamides-as-potent-and-selective-covalent-inhibitors-of-btk
#15
Richard Caldwell, Lesley Liu-Bujalski, Hui Qiu, Igor Mochalkin, Reinaldo Jones, Constantin Neagu, Andreas Goutopoulos, Roland Grenningloh, Theresa Johnson, Brian Sherer, Anna Gardberg, Ariele Viacava Follis, Federica Morandi, Jared Head
Btk is an attractive target for the treatment of a range of Bcell malignancies as well as several autoimmune diseases such as murine lupus and rheumatoid arthritis. Several covalent irreversible inhibitors of Btk are currently in development including ibrutinib which was approved for treatment of B-cell malignancies. Herein, we describe our efforts using X-ray guided structure based design (SBD) to identify a novel chemical series of covalent Btk inhibitors. The resulting pyridine carboxamides were potent and selective inhibitors of Btk having excellent enzymatic and cellular inhibitory activity...
September 27, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30290717/therapeutic-potential-of-allogeneic-mesenchymal-stromal-cells-transplantation-for-lupus-nephritis
#16
J Barbado, S Tabera, A Sánchez, J García-Sancho
Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months...
October 5, 2018: Lupus
https://www.readbyqxmd.com/read/30287776/lipopolysaccharide-challenge-reveals-hypothalamic-pituitary-adrenal-axis-dysfunction-in-murine-systemic-lupus-erythematosus
#17
Grace S Pham, Keisa W Mathis
Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands...
October 4, 2018: Brain Sciences
https://www.readbyqxmd.com/read/30287618/an-autoimmune-disease-variant-of-igg1-modulates-b-cell-activation-and-differentiation
#18
Xiangjun Chen, Sun Xiao-Lin, Wei Yang, Bing Yang, Xiaozhen Zhao, Shuting Chen, Lili He, Hui Chen, Changmei Yang, Le Xiao, Zai Chang, Jianping Guo, Jing He, Fuping Zhang, Fang Zheng, Zhibin Hu, Zhiyong Yang, Jizhong Lou, Wenjie Zheng, Hai Qi, Chenqi Xu, Hong Zhang, Hongying Shan, Xujie Zhou, Qingwen Wang, Yi Shi, Luhua Lai, Zhanguo Li, Wanli Liu
The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here, we identify a variant of human IgG1 (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog G390R knock-in mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies. This enhanced production of antibodies is also observed in hapten-immunized G390R mice, as well as in influenza-vaccinated human G396R homozygous carriers...
October 4, 2018: Science
https://www.readbyqxmd.com/read/30286201/b-cell-responses-to-apoptotic-cells-in-mfg-e8-mice
#19
YuFeng Peng
Defective clearance of apoptotic cells in MFG-E8 deficient mice results in lupus-like disease in the mixed B6x129, but not pure B6 background. The lack of overt autoimmunity in MFG-E8-/- B6 mice suggests that accumulation of apoptotic cells is not sufficient to break central tolerance. However, the delayed clearance of apoptotic cells in the follicles of MFG-E8-/- B6 mice provides an excellent opportunity to investigate how B cells respond to excessive apoptotic cells in the periphery under relatively non-inflammatory conditions...
2018: PloS One
https://www.readbyqxmd.com/read/30284593/pediatric-systemic-lupus-erythematosus-retrospective-analysis-of-clinico-laboratory-parameters-and-their-association-with-systemic-lupus-erythematosus-disease-activity-index-score
#20
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