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Lupus Science & Medicine

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https://www.readbyqxmd.com/read/30094041/dna-methylation-101-what-is-important-to-know-about-dna-methylation-and-its-role-in-sle-risk-and-disease-heterogeneity
#1
Cristina M Lanata, Sharon A Chung, Lindsey A Criswell
SLE is a complex autoimmune disease that results from the interplay of genetics, epigenetics and environmental exposures. DNA methylation is an epigenetic mechanism that regulates gene expression and tissue differentiation. Among all the epigenetic modifications, DNA methylation perturbations have been the most widely studied in SLE. It mediates processes relevant to SLE, including lymphocyte development, X-chromosome inactivation and the suppression of endogenous retroviruses. The establishment of most DNA methylation marks occurs in utero; however, a small percentage of epigenetic marks are dynamic and can change throughout a person's lifetime and in relation to exposures...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/30094040/myocarditis-in-systemic-lupus-erythematosus-diagnosed-by-18-f-fluorodeoxyglucose-positron-emission-tomography
#2
Alexandra Perel-Winkler, Sabahat Bokhari, Thania Perez-Recio, Afshin Zartoshti, Anca Askanase, Laura Geraldino-Pardilla
Objectives: Cardiovascular diseaseand heart failure (CHF) are leading causes of death in systemic lupus erythematosus (SLE). The underlying mechanisms for increased CHF in SLE are unclear but myocardial inflammation and lupus myocarditis (LM) may play a role. We propose that 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET)/CT can help diagnose LM. Methods: This report describes eight patients with presumed LM; five patients were evaluated due to active cardiorespiratory symptoms and three patients were participating in a pilot study to determine the prevalence of subclinical myocarditis in SLE...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/30094039/measuring-lupus-arthritis-activity-using-contrasted-high-field-mri-associations-with-clinical-measures-of-disease-activity-and-novel-patterns-of-disease
#3
Eric S Zollars, Madison Hyer, Bethany Wolf, Russell Chapin
Objective: Arthritis in SLE is poorly described, and there is no objective measure for quantification of arthritis. In this pilot study, we aim to assess the utility of the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for the quantification of lupus arthritis. Methods: Patients were eligible for entry into the study if they were evaluated at the Medical University of South Carolina Lupus Center and determined by their treating rheumatologist to have active hand arthritis due to SLE...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29955371/correction-lupus-community-panel-proposals-for-optimising-clinical-trials-2018
#4
(no author information available yet)
[This corrects the article DOI: 10.1136/lupus-2018-000258.].
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29955370/tnf-%C3%AE-and-plasma-albumin-as-biomarkers-of-disease-activity-in-systemic-lupus-erythematosus
#5
Helena Idborg, Susanna Eketjäll, Susanne Pettersson, Johanna T Gustafsson, Agneta Zickert, Marika Kvarnström, Vilija Oke, Per-Johan Jakobsson, Iva Gunnarsson, Elisabet Svenungsson
Objectives: Composite criteria/indices are presently used to diagnose and monitor patients with systemic lupus erythematosus (SLE). Biomarkers for these purposes would be helpful in clinical practice. We therefore evaluated a large panel of cytokines and basic laboratory tests and investigated their performance as discriminators versus controls and as biomarkers of disease activity (DA). Methods: We examined 437 patients with SLE, fulfilling American College of Rheumatology-82 criteria, and 322 matched controls...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29955369/analysis-of-relationships-between-25-hydroxyvitamin-d-parathyroid-hormone-and-cathelicidin-with-inflammation-and-cardiovascular-risk-in-subjects-with-paediatric-systemic-lupus-erythematosus-an-atherosclerosis-prevention-in-paediatric-lupus-erythematosus-apple
#6
Varsha Gupta, Vin Tangpricha, Eric Yow, Grace A McComsey, Laura Schanberg, Angela Byun Robinson
Objectives: Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE. Methods: Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29955368/immunosuppressant-use-and-hospitalisations-in-adult-patients-with-systemic-lupus-erythematosus-admitted-to-a-tertiary-academic-medical-centre
#7
Christine Anastasiou, Olivia Dulai, Amrutha Baskaran, James Proudfoot, Samuel Verhaegen, Kenneth Kalunian
Objectives: To describe how immunosuppressant use and hospitalisation patterns for SLE have evolved by comparing admission statistics at one academic centre between 2005 and 2013. Methods: We identified admissions for SLE and for all hospitalised patients by using the hospital electronic database. For adult patients with SLE, a comprehensive chart review was conducted to identify primary indications for hospitalisation, in-hospital mortality, mean length of stay and immunosuppressant use...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29868177/erythrocyte-bound-c4d-in-combination-with-complement-and-autoantibody-status-for-the-monitoring-of-sle
#8
Joan T Merrill, Michelle A Petri, Jill Buyon, Rosalind Ramsey-Goldman, Kenneth Kalunian, Chaim Putterman, John Conklin, Richard A Furie, Thierry Dervieux
Background: We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE. Methods: Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI)...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29868176/kynurenine-pathway-is-altered-in-patients-with-sle-and-associated-with-severe-fatigue
#9
Karolina Åkesson, Susanne Pettersson, Sara Ståhl, Izabella Surowiec, Mattias Hedenström, Susanna Eketjäll, Johan Trygg, Per-Johan Jakobsson, Iva Gunnarsson, Elisabet Svenungsson, Helena Idborg
Objective: Fatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29765617/accelerated-model-of-lupus-autoimmunity-and-vasculopathy-driven-by-toll-like-receptor-7-9-imbalance
#10
Yudong Liu, Nickie L Seto, Carmelo Carmona-Rivera, Mariana J Kaplan
Objectives: Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29765616/quantifying-the-burden-of-steroid-related-damage-in-sle-in-the-hopkins-lupus-cohort
#11
Julie E Davidson, Qinggong Fu, Sapna Rao, Laurence S Magder, Michelle Petri
Objective: Corticosteroids are a mainstay of SLE treatment; however, cumulative steroid exposure may lead to organ damage. This study aimed to quantify the risk of new diabetes, hypertension, cataracts, osteoporosis and avascular necrosis that is attributable to cumulative corticosteroid exposure in SLE. Methods: Using data from the Hopkins Lupus Cohort, a longitudinal study of lupus activity, organ damage and quality of life in patients with SLE, five matched case-control analyses nested within a prospectively enrolled SLE cohort were performed...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29657738/lupus-community-panel-proposals-for-optimising-clinical-trials-2018
#12
REVIEW
Joan T Merrill, Susan Manzi, Cynthia Aranow, Anca Askenase, Ian Bruce, Eliza Chakravarty, Ben Chong, Karen Costenbader, Maria Dall'Era, Ellen Ginzler, Leslie Hanrahan, Ken Kalunian, Joseph Merola, Sandra Raymond, Brad Rovin, Amit Saxena, Victoria P Werth
Formidable impediments stand in the way of treatment development for lupus. These include the unwieldy size of current trials, international competition for scarce patients, complex outcome measures and a poor understanding of these outcomes in the world at large. The heterogeneity of the disease itself coupled to superimposition of variegated background polypharmacy has created enough immunological noise to virtually ensure the failure of lupus treatment trials, leaving an understandable suspicion that at least some of the results in testing failed drugs over the years may not have been negative, but merely uninterpretable...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29644082/characterisation-of-anifrolumab-a-fully-human-anti-interferon-receptor-antagonist-antibody-for-the-treatment-of-systemic-lupus-erythematosus
#13
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/29644081/risk-of-adverse-events-from-different-drugs-for-sle-a-systematic-review-and-network-meta-analysis
#14
Jingru Tian, Yien Luo, Haijing Wu, Hai Long, Ming Zhao, Qianjin Lu
Objective: The comparative safety of immunosuppressive drugs, biologicals and glucocorticoids (GC) for patients with SLE remains controversial. We aimed to investigate the specific side effects of the available SLE drugs in this population of patients. Methods: Electronic databases were systematically searched through September 2017 for randomised trials in patients with SLE. The primary outcomes were all-cause mortality and withdrawal related to adverse events (AEs)...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29644080/safety-tolerability-and-pharmacokinetics-of-subcutaneous-and-intravenous-anifrolumab-in-healthy-volunteers
#15
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/29531773/unique-clinical-characteristics-autoantibodies-and-medication-use-in-native-american-patients-with-systemic-lupus-erythematosus
#16
Joseph M Kheir, Carla J Guthridge, Jonathon R Johnston, Lucas J Adams, Astrid Rasmussen, Timothy F Gross, Melissa E Munroe, Rebecka L Bourn, Kathy L Sivils, Joel M Guthridge, Michael H Weisman, Daniel J Wallace, Juan-Manuel Anaya, Adriana Rojas Villarraga, James N Jarvis, John B Harley, Judith A James
Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with varied morbidity and mortality. We assessed clinical presentations, autoantibody specificities and therapeutic interventions in Native American (NA) patients with SLE. Methods: Patients with SLE meeting 1997 American College of Rheumatology classification criteria (n=3148) were enrolled between 1992 and 2010 in the multiethnic, cross-sectional Lupus Family Registry and Repository...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29531772/remission-and-low-disease-activity-in-systemic-lupus-erythematosus-an-achievable-goal-even-with-fewer-steroids-real-life-data-from-a-monocentric-cohort
#17
Chiara Tani, Roberta Vagelli, Chiara Stagnaro, Linda Carli, Marta Mosca
Objectives: To evaluate what proportion of patients fulfil the DORIS definition of remission, the definition of lupus low disease activity state (LLDAS) and LLDAS with a glucocorticoid (GC) dosage ≤5 (LLDAS5) in a longitudinal monocentric cohort of patients with SLE; to identify predictors of sustained remission and LLDAS attainment; to evaluate the effect of sustained remission and LLDAS on damage accrual over a period of 5 years and compare the two conditions in terms of clinical outcomes...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29387437/associations-between-type-i-interferon-and-antiphospholipid-antibody-status-differ-between-ancestral-backgrounds
#18
Taro Iwamoto, Jessica Dorschner, Meenakshi Jolly, Xiangyang Huang, Timothy B Niewold
Objective: The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity. Methods: Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29387436/very-delayed-lupus-nephritis-a-report-of-three-cases-and-literature-review
#19
André R Alexandre, Pedro L Carreira, David A Isenberg
Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE) and is associated with a worse prognosis. LN usually develops within the first 5 years of the onset of the disease. We report three patients with very delayed LN (DLN) diagnosed after 15 or more years after SLE diagnosis. The three patients were non-Caucasian women with adolescent or adult-onset SLE. Each had antinuclear, anti-dsDNA and anti-Ro antibodies. Hydroxychloroquine was prescribed for each. Their disease courses were characterised by sporadic non-renal flares controlled by steroids and, in two cases, by one cycle of rituximab...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29387435/mouse-models-of-lupus-what-they-tell-us-and-what-they-don-t
#20
Mara Lennard Richard, Gary Gilkeson
Lupus is a complex heterogeneous disease characterised by autoantibody production and immune complex deposition followed by damage to target tissues. Animal models of human diseases are an invaluable tool for defining pathogenic mechanisms and testing of novel therapeutic agents. There are perhaps more applicable murine models of lupus than any other human disease. There are spontaneous models of lupus, inducible models of lupus, transgenic-induced lupus, gene knockout induced lupus and humanised mouse models of lupus...
2018: Lupus Science & Medicine
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