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https://www.readbyqxmd.com/read/29776017/pharmacokinetics-and-c-reactive-protein-modelling-of-anti-il-6-antibody-pf-04236921-in-healthy-volunteers-and-patients-with-autoimmune-disease
#1
Cheryl Li, Satoshi Shoji, Jean Beebe
AIMS: The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included...
May 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775752/the-genetics-and-molecular-pathogenesis-of-systemic-lupus-erythematosus-sle-in-populations-of-different-ancestry
#2
REVIEW
George N Goulielmos, Maria I Zervou, Vassilis M Vazgiourakis, Yogita Ghodke-Puranik, Alexandros Garyfallos, Timothy B Niewold
Systemic lupus erythematosus (SLE; OMIM 152700) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and a multi-system involvement commonly affecting the skin, renal, musculoskeletal, and hematopoetic systems clinical manifestations involving. Disease features range from mild manifestations, such as rash or arthritis, to life-threatening end-organ manifestations, such as glomerulonephritis or thrombosis, and it is difficult to predict which manifestations will affect a given patient...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775619/proteomic-approach-to-profiling-immune-complex-antigens-in-cerebrospinal-fluid-samples-from-patients-with-central-nervous-system-autoimmune-diseases
#3
Nozomi Aibara, Kunihiro Ichinose, Miyako Baba, Hideki Nakajima, Katsuya Satoh, Ryuichiro Atarashi, Naoya Kishikawa, Noriyuki Nishida, Atsushi Kawakami, Naotaka Kuroda, Kaname Ohyama
BACKGROUND: Immune complexes (ICs) may clearly reflect immunological abnormalities caused by disease, especially for autoimmune diseases. Although ICs have been detected in cerebrospinal fluid (CSF) from patients with CNS autoimmune diseases, identities of antigens in such ICs have not been comprehensively determined. METHODS: We used immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, to characterize ICs in CSF samples from patients with CNS autoimmune diseases, and to find disease-specific IC antigen to a certain CNS autoimmune disease...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29774953/dermoscopic-patterns-of-filiform-papillae-of-the-tongue-in-patients-with-and-without-connective-tissue-autoimmune-diseases
#4
José Manuel Díaz-González, María E Vega-Memije, Adalberto Mosqueda-Taylor, Víctor Noé García-Edgar, Juan Carlos Cuevas-González
BACKGROUND: Connective tissue autoimmune diseases (CTADs) constitute a group of conditions, including rheumatoid arthritis; systemic lupus erythematosus; mixed connective tissue disease; calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome; scleroderma; dermatomyositis; and Sjögren syndrome. There are few studies on the alterations in filiform papillae in CTAD. Thus, the objective of this work was to determine whether there are changes in the macroscopic and dermoscopic patterns of filiform papillae...
May 18, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#5
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29774490/higher-activation-of-the-interferon-gamma-signaling-pathway-in-systemic-lupus-erythematosus-patients-with-a-high-type-i-ifn-score-relation-to-disease-activity
#6
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29773465/pulmonary-manifestations-in-systemic-lupus-erythematosus-pleural-involvement-acute-pneumonitis-chronic-interstitial-lung-disease-and-diffuse-alveolar-hemorrhage
#7
Georgina Aguilera-Pickens, Carlos Abud-Mendoza
Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach...
May 14, 2018: Reumatología Clinica
https://www.readbyqxmd.com/read/29773269/juvenile-onset-systemic-lupus-erythematosus-jsle-pathophysiological-concepts-and-treatment-options
#8
REVIEW
Christian M Hedrich, Eve M D Smith, Michael W Beresford
The systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) manifests before the age of 16 years in 10-20% of all cases. Clinical courses are more severe, and organ complications are more common in patients with juvenile SLE. Varying gender distribution in different age groups and increasing severity with younger age and the presence of monogenic disease in early childhood indicate distinct differences in the pathophysiology of juvenile versus adult-onset SLE. Regardless of these differences, classification criteria and treatment options are identical...
August 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29773266/genetic-interferonopathies-an-overview
#9
REVIEW
Despina Eleftheriou, Paul A Brogan
Interferonopathies comprise an expanding group of monogenic diseases characterised by disturbance of the homeostatic control of interferon (IFN)-mediated immune responses. Although differing in the degree of phenotypic expression and severity, the clinical presentation of these diseases shows a considerable degree of overlap, reflecting their common pathogenetic mechanisms. Increased understanding of the molecular basis of these Mendelian disorders has led to the identification of targeted therapies for these diseases, which could also be of potential relevance for non-genetic IFN-mediated diseases such as systemic lupus erythematosus and juvenile dermatomyositis...
August 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29771216/mindfulness-based-cognitive-hypnotherapy-and-skin-disorders
#10
Philip D Shenefelt
Mindfulness-based cognitive hypnotherapy integrates mindfulness, cognitive-behavioral therapy, and hypnotherapy to improve physical, emotional, mental, and/or spiritual aspects of skin disorders. Meditation, including mindfulness meditation, and hypnosis both utilize trance phenomena to help produce focalization and specific improvements in skin disorders through psycho-neuro-endocrine-immunologic mechanisms. Hypnosis, cognitive hypnotherapy, focused meditation, and mindfulness meditation are discussed with respect to improving various skin disorders including acne, acne excoriée, alopecia areata, atopic dermatitis, congenital ichthyosiform erythroderma, dyshidrotic dermatitis, erythema nodosum, erythromelalgia, furuncles, glossodynia, herpes simplex, hyperhidrosis, ichthyosis vulgaris, lichen planus, neurodermatitis, nummular dermatitis, postherpetic neuralgia, prurigo nodularis, pruritus, psoriasis, rosacea, trichotillomania, urticaria, verruca vulgaris, and vitiligo...
July 2018: American Journal of Clinical Hypnosis
https://www.readbyqxmd.com/read/29771193/early-symptoms-of-systemic-lupus-erythematosus-sle-recalled-by-339-sle-patients
#11
N Leuchten, B Milke, B Winkler-Rohlfing, D Daikh, T Dörner, S R Johnson, M Aringer
Objective The European League Against Rheumatism and the American College of Rheumatology jointly embarked on a new classification criteria for systemic lupus erythematosus (SLE) project. Its first phase involved generation of a broad set of items potentially useful for classification of SLE. This study was undertaken to add the patient perspective to an expert Delphi approach and an early patient cohort study. Methods A national cross-sectional study was conducted. A self-report questionnaire was published in the "Schmetterling" (Butterfly), the quarterly journal of the German SLE patient association...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29770567/association-between-polymorphisms-in-the-promoter-region-of-mir-17-92-cluster-and-systemic-lupus-erythematosus-in-a-chinese-population
#12
Rong Wang, Chun-Fang Wang, Hai-Mei Qin, Yu-Lan Lu, Gui-Jiang Wei, Hua-Tuo Huang, Yang Xiang, Jun-Li Wang, Yan Lan, Ye-Sheng Wei
The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR-17-92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR-17-92 was measured by quantitative real-time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46-0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46-0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0...
May 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29769526/a-whole-genome-sequence-study-identifies-genetic-risk-factors-for-neuromyelitis-optica
#13
Karol Estrada, Christopher W Whelan, Fengmei Zhao, Paola Bronson, Robert E Handsaker, Chao Sun, John P Carulli, Tim Harris, Richard M Ransohoff, Steven A McCarroll, Aaron G Day-Williams, Benjamin M Greenberg, Daniel G MacArthur
Neuromyelitis optica (NMO) is a rare autoimmune disease that affects the optic nerve and spinal cord. Most NMO patients ( > 70%) are seropositive for circulating autoantibodies against aquaporin 4 (NMO-IgG+). Here, we meta-analyze whole-genome sequences from 86 NMO cases and 460 controls with genome-wide SNP array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total N = 215 NMO cases, 1244 controls). We identify two independent signals in the major histocompatibility complex (MHC) region associated with NMO-IgG+, one of which may be explained by structural variation in the complement component 4 genes...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769437/exosome-delivered-micrornas-promote-ifn-%C3%AE-secretion-by-human-plasmacytoid-dcs-via-tlr7
#14
Valentina Salvi, Veronica Gianello, Sara Busatto, Paolo Bergese, Laura Andreoli, Ugo D'Oro, Alessandra Zingoni, Angela Tincani, Silvano Sozzani, Daniela Bosisio
The excessive production of type I IFNs is a hallmark and a main pathogenic mechanism of many autoimmune diseases, including systemic lupus erythematosus (SLE). In these pathologies, the sustained secretion of type I IFNs is dependent on the improper activation of plasmacytoid DCs (pDCs) by self-nucleic acids. However, the nature and origin of pDC-activating self-nucleic acids is still incompletely characterized. Here, we report that exosomes isolated from the plasma of SLE patients can activate the secretion of IFN-α by human blood pDCs in vitro...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29767288/therapeutic-applications-of-mesenchymal-stem-cells-for-systemic-lupus-erythematosus
#15
Jianyong Xu
Mesenchymal stem cells (MSCs) have been intensively studied and applied in regenerative medicine and tissue engineering. Recently, their immune modulation functions make them as attractive potential approaches for autoimmune disease treatment. Systemic lupus erythematosus (SLE) is one type of chronic autoimmune diseases with multi-organ damaged by the immune system. Although current available treatments are effective for some patients, others are refractory for these therapies. The immuno-modulatory and regenerative characteristics of MSCs make them as one promising candidate for treating SLE...
May 17, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29766809/associations-between-depressive-disorders-and-inflammatory-rheumatic-diseases
#16
Ozkan Varan, Hakan Babaoglu, Berna Goker
Depressive disorders, are not only common but also among the leading causes of disability worldwide. They are associated with increased incidences of various other diseases. It has been shown that in patients with autoimmune diseases, when depression coexists, the quality of life is worse and medical treatment and management is compromised. Depression-like symptoms, such as fatigue and disinterest are also common in inflammatory rheumatic diseases and often associated with poor quality of life. Medical therapy targeting inflammation results in alleviation of these symptoms in many patients...
May 15, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29766530/population-pharmacokinetics-of-tacrolimus-in-paediatric-systemic-lupus-erythematosus-based-on-real-world-study
#17
D-D Wang, J-M Lu, Q Li, Z-P Li
WHAT IS KNOWN AND OBJECTIVES: Different population pharmacokinetics (PPK) models of tacrolimus have been established in various populations. However, the tacrolimus PPK model in paediatric systemic lupus erythematosus (PSLE) is still undefined. This study aimed to establish the tacrolimus PPK model in Chinese PSLE. METHODS: A total of nineteen Chinese patients with PSLE from real-world study were characterized with nonlinear mixed-effects modelling (NONMEM). The impact of demographic features, biological characteristics, and concomitant medications was evaluated...
May 15, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29766256/monogenic-systemic-lupus-erythematosus-insights-in-pathophysiology
#18
REVIEW
Ezgi Deniz Batu
Systemic lupus erythematosus (SLE) is a complex disease with different genetic, immunologic, and environmental factors contributing to the pathogenesis. Monogenic SLE could help us understand the main phases of immune dysregulation in SLE. The aim of this review is to summarize the current knowledge on monogenic SLE with the implications of the respective genes on disease pathogenesis. A comprehensive literature search on monogenic SLE was conducted utilizing the Cochrane Library and MEDLINE/PubMed databases...
May 15, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29765992/serological-immunoglobulin-free-light-chain-profile-in-myasthenia-gravis-patients
#19
Umberto Basile, Mariapaola Marino, Cecilia Napodano, Krizia Pocino, Paolo Emilio Alboini, Francesca Gulli, Amelia Evoli, Carlo Provenzano, Emanuela Bartoccioni
Background: Serological levels of free immunoglobulin light chains (FLCs), produced in excess of heavy chains during synthesis of immunoglobulins by plasma cells, can be considered a direct marker of B cell activity in different systemic inflammatory-autoimmune conditions and may represent a useful predictor of rituximab (RTX) therapeutic efficacy, as reported for rheumatoid arthritis and systemic lupus erythematosus. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction with antibodies (abs) targeting the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK), inducing muscle weakness and excessive fatigability...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765617/accelerated-model-of-lupus-autoimmunity-and-vasculopathy-driven-by-toll-like-receptor-7-9-imbalance
#20
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
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