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Lupus Science & Medicine

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https://www.readbyqxmd.com/read/29868177/erythrocyte-bound-c4d-in-combination-with-complement-and-autoantibody-status-for-the-monitoring-of-sle
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/29344387/repository-corticotropin-injection-in-patients-with-persistently-active-sle-requiring-corticosteroids-post-hoc-analysis-of-results-from-a-two-part-52-week-pilot-study
#14
Richard A Furie, Margaret Mitrane, Enxu Zhao, Patrice M Becker
Objective: Post hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks. Methods: Patients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1-3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29344386/current-and-future-therapies-for-sle-obstacles-and-recommendations-for-the-development-of-novel-treatments
#15
REVIEW
Zahi Touma, Dafna D Gladman
SLE is a serious, debilitating autoimmune disease that affects various organs and body systems. Of all the heterogeneous autoimmune diseases, SLE is perhaps the most heterogeneous. Patients with SLE, who are primarily female, have diverse disease manifestations and severity. SLE is characterised by substantial concentrations of autoantibodies against nuclear antigens, which are thought to be caused by immune cell dysregulation. Until recently, several immunosuppressant agents were used to treat this disease...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29259790/complement-levels-and-risk-of-organ-involvement-in-patients-with-systemic-lupus-erythematosus
#16
Ignacio Javier Gandino, Marina Scolnik, Emmanuel Bertiller, Valeria Scaglioni, Luis Jose Catoggio, Enrique Roberto Soriano
Objective: Complement plays a major role in SLE. Complement participation has been linked to disease activity and damage. Our objective was to estimate the association of complement behaviour with clinical manifestations, visceral injury and mortality in patients with SLE. Methods: Complement determinations (C3 and C4 levels) were analysed in patients with SLE (fulfilling American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC)criteria) seen at a university hospital between 2000 and 2013...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29238603/early-proteinuria-response-a-valid-real-life-situation-predictor-of-long-term-lupus-renal-outcome-in-an-ethnically-diverse-group-with-severe-biopsy-proven-nephritis
#17
Michelle R Ugolini-Lopes, Luciana Parente C Seguro, Maitê Xavier F Castro, Danielle Daffre, Alex C Lopes, Eduardo F Borba, Eloisa Bonfá
Objective: Two recent important lupus nephritis trials reported that proteinuria was a good predictor of renal outcome in Caucasians, but data on real-life situation, other races and severe nephritis are lacking to substantiate this finding as a simple test to guide clinical practice. The aim of this study was to validate proteinuria as a predictor of long-term renal outcome in real-life situation in a racially diverse group of patients with severe nephritis. Methods: Proteinuria, serum creatinine (SCr) and urine red blood cells were assessed at baseline and after 3, 6 and 12 months, as early predictors of long-term renal outcome (SCr <1...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29238602/single-cell-gene-expression-patterns-in-lupus-monocytes-independently-indicate-disease-activity-interferon-and-therapy
#18
Zhongbo Jin, Wei Fan, Mark A Jensen, Jessica M Dorschner, George F Bonadurer, Danielle M Vsetecka, Shreyasee Amin, Ashima Makol, Floranne Ernste, Thomas Osborn, Kevin Moder, Vaidehi Chowdhary, Timothy B Niewold
Objectives: Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features. Methods: Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29238601/clinicians-approaches-to-management-of-background-treatment-in-patients-with-sle-in-clinical-remission-results-of-an-international-observational-survey
#19
Pintip Ngamjanyaporn, Eoghan M McCarthy, Jamie C Sergeant, John Reynolds, Sarah Skeoch, Benjamin Parker, Ian N Bruce
Background: The definition of remission in systemic lupus erythematosus (SLE) remains unclear, especially how background treatment should be interpreted. Objective: To determine preferences of clinicians in treatment of patients in clinical remission from SLE and to assess how previous severity, duration of remission and serology influence changes in treatment. Methods: We undertook an internet-based survey of clinicians managing patients with SLE...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29214038/cell-bound-complement-activation-products-in-sle
#20
REVIEW
Rosalind Ramsey-Goldman, Jian Li, Thierry Dervieux, Roberta Vezza Alexander
Diagnosis of SLE is based on clinical manifestations and laboratory findings. Timely diagnosis and treatment are important to control disease activity and prevent organ damage. However, diagnosis is challenging because of the heterogeneity in clinical signs and symptoms, and also because the disease presents with alternating periods of flare and quiescence. As SLE is an autoimmune disease characterised by the formation of autoantibodies, diagnostic immunology laboratory tests for detecting and quantifying autoantibodies are commonly used for the diagnosis and classification of SLE...
2017: Lupus Science & Medicine
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