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Different types of lupus

Pei-Hui Wang, Sin-Yee Fung, Wei-Wei Gao, Jian-Jun Deng, Yun Cheng, Vidyanath Chaudhary, Kit-San Yuen, Ting-Hin Ho, Ching-Ping Chan, Yan Zhang, Kin-Hang Kok, Wanling Yang, Chi-Ping Chan, Dong-Yan Jin
STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2'3'-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production...
March 14, 2018: Nucleic Acids Research
Carlos Perez-Sánchez, Iván Arias-de la Rosa, María Ángeles Aguirre, María Luque-Tévar, Patricia Ruiz-Limón, Nuria Barbarroja, Yolanda Jiménez-Gómez, María Carmen Ábalos-Aguilera, Eduardo Collantes-Estévez, Pedro Segui, Francisco Velasco, María Teresa Herranz, Jesús Lozano-Herrero, María Julia Hernandez-Vidal, Constantino Martínez, Rocío González-Conejero, Massimo Radin, Savino Sciascia, Irene Cecchi, María José Cuadrado, Chary López-Pedrera
The present study aimed at identifying the plasma miRNA profile of antiphospholipid syndrome patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. Ninety antiphospholipid syndrome patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of antiphospholipid syndrome patients allowed identifying a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic Regression and ROC-curve analyses identified a signature of 10 miRNA ratios as biomarkers of disease...
March 15, 2018: Haematologica
Felix Lauffer, Manja Jargosch, Linda Krause, Natalie Garzorz-Stark, Regina Franz, Sophie Roenneberg, Alexander Böhner, Nikola S Mueller, Fabian J Theis, Carsten B Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
Interface dermatitis (ID) is a characteristic histological pattern which occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different ID positive skin diseases, lichen planus (LP) and lupus erythematosus (LE). The shared transcriptome signature pointed towards a strong type I immune response and biopsy derived T cells were dominated by IFN-γ and TNF-α positive cells...
March 8, 2018: Journal of Investigative Dermatology
Lora J Kasselman, Nicholas A Vernice, Joshua DeLeon, Allison B Reiss
Cardiovascular disease associated with obesity and autoimmunity is the leading cause of death in these populations and significant residual risk remains despite current treatment approaches. Obesity, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are linked to chronic inflammation, and subjects with these disorders have characteristic shifts in their gut microbiome composition. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting cardiovascular disease...
March 2, 2018: Atherosclerosis
Yue Yang, Zheng Zhang, Li Zhuo, Da-Peng Chen, Wen-Ge Li
Background: Chronic kidney disease has become a leading public health concern in China, as it is associated with increased morbidity, mortality, and costs. However, the overall situation regarding common glomerular diseases in China remains unclear. Hence, the aim of this study was to assess the national profile of the common types of glomerulonephritis in China. Methods: We searched Medline, Embase, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases for English and Chinese language articles from inception to September 2017...
March 20, 2018: Chinese Medical Journal
Boya Zhang, Xianzhen Chen, Qiang Zhou, Yinjing Song, Siyuan Sun, Hao Cheng
OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. HPV6b is a low-risk type of HPVs that causes benign verrucous hyperplastic lesions of the skin and anal genital mucosa. Previous research has indicated that HPV genotype 6 is sometimes associated with high-grade lesions and anal cancer. The pathogenesis of low-risk HPV infection and its relationship to high-risk HPV is not clear at present. The E7 protein, which is encoded by HPV early -expressing genes, plays an important role in HPV infection...
March 1, 2018: Gene
Clive Kearon, Sameer Parpia, Fredrick A Spencer, Trevor Baglin, Scott M Stevens, Kenneth A Bauer, Steven R Lentz, Craig M Kessler, James D Douketis, Stephan Moll, Scott Kaatz, Sam Schulman, Jean M Connors, Jeffrey S Ginsberg, Luciana Spadafora, Vinai Bhagirath, Patricia C Liaw, Jeffrey I Weitz, Jim A Julian
It is uncertain whether antiphospholipid antibodies (APA) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-β2 glycoprotein I antibodies and lupus anticoagulant on two occasions about six months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APA were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results...
February 28, 2018: Blood
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
K L Connelly, R Kandane-Rathnayake, M Huq, A Hoi, M Nikpour, E F Morand
Type I interferon (IFN) pathways are significant in SLE pathogenesis. Less is known about the utility of measuring markers of IFN activity in patients, or whether patient subsets with different profiles exist. We explored the longitudinal associations of IFN-induced chemokines with disease activity in a cohort of SLE patients. We calculated a validated composite score (IFN-CK) of three type I IFN-inducible chemokines (CCL2/CXCL10/CCL19) measured in 109 SLE patients (median 7 occasions over 3.2 years). Longitudinal associations of IFN-CK score with disease activity (SLEDAI-2K) and other variables were assessed using general estimating equation (GEE) methods...
February 19, 2018: Scientific Reports
Konrad Haberland, Jochen A Ackermann, Natacha Ipseiz, Stephan Culemann, Katharina Pracht, Matthias Englbrecht, Hans-Martin Jäck, Georg Schett, Wolfgang Schuh, Gerhard Krönke
Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. Contrary to our expectations and the currently prevailing paradigm, we found that eosinophils are fully dispensable for the survival of murine bone marrow plasma cells and accordingly do not contribute to antibody production and autoantibody-mediated disease...
February 14, 2018: European Journal of Immunology
Keith B Elkon
Cells of the innate immune system are rigged with sensors that detect nucleic acids derived from microbes, especially viruses. It has become clear that these same sensors that respond to nucleic acids derived from damaged cells or defective intracellular processing are implicated in triggering diseases such as lupus and arthritis. The ways in which cells die and the concomitant presence of proteins and peptides that allow nucleic acids to re-enter cells profoundly influence innate immune responses. This review briefly discusses different types of programmed necrosis such as pyroptosis, necroptosis and NETosis and explains how nucleic acids can engage intracellular receptors and stimulate inflammation...
February 13, 2018: Arthritis & Rheumatology
John J Sim, Simran K Bhandari, Michael Batech, Aviv Hever, Teresa N Harrison, Yu-Hsiang Shu, Dean A Kujubu, Tracy Y Jonelis, Michael H Kanter, Steven J Jacobsen
OBJECTIVE: To compare renal function decline, incident end-stage renal disease (ESRD), and mortality among patients with 5 common glomerular diseases in a large diverse population. PATIENTS AND METHODS: A retrospective cohort study (between January 1, 2000, and December 31, 2011) of patients with glomerulonephropathy using the electronic health record of an integrated health system was performed. Estimated glomerular filtration rate (eGFR) change, incident ESRD, and mortality were compared among patients with biopsy-proven focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and lupus nephritis (LN)...
January 9, 2018: Mayo Clinic Proceedings
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
Jessica Perego, Andreia Mendes, Clarisse Bourbon, Voahirana Camosseto, Alexis Combes, Hong Liu, Thien-Phong Vu Manh, Alexandre Dalet, Lionel Chasson, Lionel Spinelli, Nathalie Bardin, Laurent Chiche, Manuel A S Santos, Evelina Gatti, Philippe Pierre
Endoplasmic reticulum (ER) stress triggers or amplifies inflammatory signals and cytokine production in immune cells. Upon the resolution of ER stress, the inducible phosphatase 1 cofactor GADD34 promotes the dephosphorylation of the initiation factor eIF2α, thereby enabling protein translation to resume. Several aminoguanidine compounds, such as guanabenz, perturb the eIF2α phosphorylation-dephosphorylation cycle and protect different cell or tissue types from protein misfolding and degeneration. We investigated how pharmacological interference with the eIF2α pathway could be beneficial to treat autoinflammatory diseases dependent on proinflammatory cytokines and type I interferons (IFNs), the production of which is regulated by GADD34 in dendritic cells (DCs)...
January 23, 2018: Science Signaling
Constance J Ulff-Møller, Fazila Asmar, Yi Liu, Anders J Svendsen, Florence Busato, Kirsten Grønbaek, Jörg Tost, Søren Jacobsen
OBJECTIVE: Systemic lupus erythematosus (SLE) has limited monozygotic (MZ) twin concordance, implying a role for other pathogenic factors than genetic variation, such as epigenetic changes. Using the disease discordant twin model, we investigated genome-wide DNA methylation changes in sorted CD4+ T-cells, monocytes, granulocytes and B-cells in twin pairs with at least one SLE-affected twin. METHODS: Peripheral blood from 15 SLE twin pairs (six MZ, nine dizygotic (DZ)) was processed using gradient density centrifugation for the granulocyte fraction...
January 23, 2018: Arthritis & Rheumatology
Stefan Markus Weiner
Renal involvement is common and heterogenous in connective tissue diseases and has a main influence on prognosis and mortality. In systemic lupus erythematosus proliferative glomerulonephritis is the most common manifestation, while in primary Sjogren's syndrome interstitial nephritis with tubular dysfunction is the predominant pathological feature. In systemic sclerosis the most serious renal manifestation is scleroderma renal crisis characterized by abrupt onset of hypertension and acute kidney injury associated with an increase in plasma renin activity...
January 2018: Deutsche Medizinische Wochenschrift
Hsing-Jou Su, An-Yu Cheng, Cheng-Han Liu, Chia-Bau Chu, Chaw-Ning Lee, Chao-Kai Hsu, Julia Yu-Yun Lee, Chao-Chun Yang
Primary scarring alopecia (PSA) is caused by irreversible damage to the hair epithelial stem cells that reside in hair follicles. There is limited published work regarding PSA amongst the Asian population. The aim of this study was to evaluate the clinical features and to characterize the subtypes of PSA in southern Taiwan. In this retrospective case series, we reviewed 89 patients with pathology-confirmed PSA. The data was collected from National Cheng Kung University Hospital between 1988 through 2016. The clinical and histological data were reviewed, and the patients were characterized into different subtypes of PSA based on the clinical features and histological findings...
January 16, 2018: Journal of Dermatology
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
Chi Chiu Mok, Samar Soliman, Ling Yin Ho, Fatma A Mohamed, Faten Ismail Mohamed, Chandra Mohan
BACKGROUND: The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). METHOD: Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine...
January 11, 2018: Arthritis Research & Therapy
K R Tallbacka, T Pettersson, E Pukkala
OBJECTIVE: The aim of this study was to assess the cancer risk in a cohort of Finnish patients with systemic lupus erythematosus (SLE) when followed over the long term. METHOD: The cohort consisted of 182 female and 23 male SLE patients treated at the Helsinki University Central Hospital from 1967 to 1987. The cohort was linked to the Finnish Cancer Registry and followed for cancer incidence from 1967 to 2013. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cases by the number of expected cases for different types of cancer...
January 10, 2018: Scandinavian Journal of Rheumatology
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