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SLE and dsDNA

Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
Jill Buyon, Richard Furie, Chaim Putterman, Rosalind Ramsey-Goldman, Kenneth Kalunian, Derren Barken, John Conklin, Thierry Dervieux
BACKGROUND: The relationship between cell-bound complement activation products (CB-CAPs: EC4d, EC3d), anti-C1q, soluble complement C3/C4 and disease activity in systemic lupus erythematosus (SLE) was evaluated. METHODS: Per protocol, at baseline all SLE subjects enrolled in this longitudinal study presented with active disease and elevated CB-CAPs. At each monthly visit, the non-serological (ns) Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG)-2004 index scores were determined as was a random urinary protein to creatinine ratio (uPCR)...
2016: Lupus Science & Medicine
Z H Wang, W Zhang, Y Q Zhang, C Y Pang, Y F Wang
OBJECTIVE: To observe the effect of CD40 siRNA on expression of IFN-γ, IL-17, IL-4 and anti-dsDNA antibody of systemic lupus erythematosus (SLE) animal model MRL/Lpr mice and to discuss its therapy on MRL/Lpr mice. METHODS: In the study, 16 female MRL/Lpr mice were randomly divided into control group (n=4), empty vector group (n=4), CD40-siRNA1 group (n=4) and CD40-siRNA2 group (n=4). The vectors expressing siRNA against CD40 were injected by tail veil into MRL/Lpr mice, while MRL/Lpr mice in control group and empty vector group were injected with the same dose of PBS and pGFP-V-RS vector respectively...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Vandana Pradhan, Pallavi Pandit, Anjali Rajadhyaksha, Manisha Patwardhan, Prathamesh Surve, Pradnya Kamble, Maxime Lecerf, Jagadeesh Bayry, Srinivas Kaveri, K Ghosh, Milind Y Nadkar
OBJECTIVE: To identify the hematological manifestations and its association with serum ferritin levels in SLE patients from Western India. METHODS: Ninety clinically diagnosed SLE patients fulfilling ACR criteria were included. Disease activity was assessed at the time of evaluation using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sera were tested for serum ferritin levels by ELISA (Calbiotech, USA). Autoantibodies such as ANA, anti-dsDNA by indirect immunofluorescence test (IFA- Bio-Rad, USA) and anti-cardiolipin antibodies (ACA) to IgG and IgM isotypes and Anti-β2 GP antibodies to IgG and IgM isotypes were detected by ELISA using commercially available kits (Euroimmun, Lubeck, Germany)...
May 2016: Journal of the Association of Physicians of India
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. METHODS: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors...
October 9, 2016: Arthritis & Rheumatology
Filomena Panza, Maria Claudia Alcaro, Fiorella Petrelli, Francesca Angelotti, Federico Pratesi, Paolo Rovero, Paola Migliorini
BACKGROUND: The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae minicircles, complexed with histone peptides...
October 4, 2016: Arthritis Research & Therapy
H Merwald-Fraenk, F Wiesent, R Dörfler, C Goebel
A 25-year-old Caucasian female patient presented with fever and cervical lymphadenopathy. Laboratory findings showed elevated signs of inflammation, elevated ANA titer and strongly positive anti-dsDNA antibodies. The histopathology of the lymph nodes revealed distinct features of Kikuchi-Fujimoto disease, a benign, self-limiting lymphadenopathy that typically affects young Asian females. In the literature a coincidental occurrence of Kikuchi-Fujimoto disease and systemic lupus erythematosus (SLE) is well documented...
September 30, 2016: Zeitschrift Für Rheumatologie
S Bernatsky, R Ramsey-Goldman, M Petri, M B Urowitz, D D Gladman, P F Fortin, E Ginzler, J Romero-Diaz, C Peschken, S Jacobsen, J G Hanly, C Gordon, O Nived, E H Yelin, D Isenberg, A Rahman, S-C Bae, L Joseph, T Witte, G Ruiz-Irastorza, C Aranow, D Kamen, G Sturfeldt, W D Foulkes, J E Hansen, Y St Pierre, P Chrétien Raymer, B Tessier-Cloutier, A E Clarke
OBJECTIVE: There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. METHODS: We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration...
September 29, 2016: Lupus
Tian Qian, Fangru Chen, Xiaowei Shi, Jian Li, Min Li, Yan Chen, Fei Hao, Dongmei Zhang
OBJECTIVES: We aimed to examine CCAAT/enhancer-binding protein β (C/EBP β), TNF-alpha-induced protein 3 (TNFAIP3), and TNFAIP3-interacting protein 1 (TNIP1) expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients to assess their relationship in SLE pathogenesis. METHODS: C/EBP β, TNIP1, and TNFAIP3 expression was assessed in PBMCs from 20 SLE patients and 20 controls by western blotting. The correlation between C/EBP β/TNFAIP3/TNIP1 expression and SLE disease activity was determined by Spearman's rank...
September 23, 2016: Modern Rheumatology
Johannes C Nossent, Warren D Raymond, Gro Østli Eilertsen
BACKGROUND: von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. METHODS: Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry...
2016: Lupus Science & Medicine
Iman H Bassyouni, Samar Fawzi, Tamer A Gheita, Rasha H Bassyouni, Aml S Nasr, Samah A El Bakry, Naglaa Afifi
A triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily with an established role in innate and adaptive immune response. We aimed to determine the plasma concentrations and clinical association of sTREM-1 in Systemic Lupus Erythematosus (SLE) patients. Plasma from 79 SLE patients and 35 normal healthy subjects were assayed for sTREM-1 and IL-6 levels using Enzyme Linked Immunosorbant Assay (ELISA). The clinical disease characteristics and serological data were prospectively assessed...
September 20, 2016: Immunological Investigations
Vivek Joseph, Rahul Anil, Sary Aristy
A 70-year-old man presented with complaints of rapid cognitive decline and new onset leukopenia. The patient had a 17-year history of refractory seizures. Detailed review of symptoms and investigations revealed the patient met American College of Rheumatology (ACR) diagnostic criteria for systemic lupus erythematosus (SLE). The patient had high titer ANA with a strongly positive dsDNA. Immunosuppressive therapy with hydroxychloroquine and mycophenolate mofetil led to significant improvement in cognition and seizures...
October 2016: Journal of Clinical Medicine Research
Maëlle Plawecki, Elise Lheritier, Giovanna Clavarino, Noémie Jourde-Chiche, Saber Ouili, Stéphane Paul, Evelyne Gout, Françoise Sarrot-Reynauld, Nathalie Bardin, Pierre-Yves Boëlle, Laurent Chiche, Laurence Bouillet, Nicole M Thielens, Jean-Yves Cesbron, Chantal Dumestre-Pérard
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection...
2016: PloS One
Ranjan Gupta, Akhilesh Yadav, Amita Aggarwal
Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3 months for 1 year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls...
November 2016: Clinical Rheumatology
Pragya Yadav, Matthew T Carr, Ruby Yu, Alice Mumbey-Wafula, Linda A Spatz
INTRODUCTION: The Epstein Barr Virus (EBV) has been associated with the autoimmune disease, Systemic Lupus Erythematosus (SLE). EBV nuclear antigen-I (EBNA-1) is the major nuclear protein of EBV. We previously generated an IgG monoclonal antibody (MAb) to EBNA-1, 3D4, and demonstrated that it cross-reacts with double stranded DNA (dsDNA) and binds the 148 amino acid viral binding site (VBS) in the carboxyl region of EBNA-1. The aim of the present study was to characterize another antibody to EBNA-1 that cross-reacts with dsDNA, compare its immunoglobulin genes to 3D4, and finely map the epitope in EBNA-1 that is recognized by these cross-reactive antibodies...
September 2016: Immunity, Inflammation and Disease
Sonya VanPatten, Shan Sun, Mingzhu He, Kai Fan Cheng, Ahmad Altiti, Angelos Papatheodorou, Czeslawa Kowal, Venkatesh Jeganathan, James M Crawford, Ona Bloom, Bruce T Volpe, Christian Grant, Nathalie Meurice, Thomas R Coleman, Betty Diamond, Yousef Al-Abed
Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics...
October 13, 2016: Journal of Medicinal Chemistry
Megan E B Clowse, Daniel J Wallace, Richard A Furie, Michelle A Petri, Marilyn C Pike, Piotr Leszczyński, C Michael Neuwelt, Kathryn Hobbs, Mauro Keiserman, Liliana Duca, Kenneth C Kalunian, Catrinel Galateanu, Sabine Bongardt, Christian Stach, Carolyn Beaudot, Brian Kilgallen, Caroline Gordon
Objective Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in B cells. We report data from two Phase 3, randomized, double-blind, placebo-controlled studies of epratuzumab in patients with moderately to severely active SLE; EMBODY 1 (NCT01262365) and EMBODY 2 (NCT01261793). Methods Patients met ≥4 ACR revised criteria, were ANA and/or anti-dsDNA positive, had SLEDAI-2K score ≥6, BILAG-2004 ≥1 A or ≥2 Bs in mucocutaneous, musculoskeletal or cardiorespiratory domains, and were receiving standard therapy (ST) including mandatory corticosteroids (5-60 mg/day)...
September 6, 2016: Arthritis & Rheumatology
Nicklas N Poulsen, Morten E Pedersen, Jesper Østergaard, Nickolaj J Petersen, Christoffer T Nielsen, Niels H H Heegaard, Henrik Jensen
Detection of immune responses is important in the diagnosis of many diseases. For example, the detection of circulating autoantibodies against double-stranded DNA (dsDNA) is used in the diagnosis of Systemic Lupus Erythematosus (SLE). It is, however, difficult to reach satisfactory sensitivity, specificity, and accuracy with established assays. Also, existing methodologies for quantification of autoantibodies are challenging to transfer to a point-of-care setting. Here we present the use of flow-induced dispersion analysis (FIDA) for rapid (minutes) measurement of autoantibodies against dsDNA...
September 20, 2016: Analytical Chemistry
Theresa R Wilhelm, Laurence S Magder, Michelle Petri
INTRODUCTION: Remission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission. METHODS: We applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT...
August 24, 2016: Annals of the Rheumatic Diseases
Huai-Chia Chuang, Yi-Ming Chen, Wei-Ting Hung, Ju-Pi Li, Der-Yuan Chen, Joung-Liang Lan, Tse-Hua Tan
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls...
August 19, 2016: Oncotarget
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