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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/28549776/methylome-and-transcriptome-profiling-in-myasthenia-gravis-monozygotic-twins
#1
Shimrat Mamrut, Nili Avidan, Frédérique Truffault, Elsebeth Staun-Ram, Tarek Sharshar, Bruno Eymard, Mélinée Frenkian, Jiri Pitha, Marc de Baets, Laurent Servais, Sonia Berrih-Aknin, Ariel Miller
OBJECTIVE: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. METHODS: The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples...
May 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28545737/microrna-146a-governs-fibroblast-activation-and-joint-pathology-in-arthritis
#2
Victoria Saferding, Antonia Puchner, Eliana Goncalves-Alves, Melanie Hofmann, Michael Bonelli, Julia S Brunner, Emine Sahin, Birgit Niederreiter, Silvia Hayer, Hans P Kiener, Elisa Einwallner, Ramzi Nehmar, Raphael Carapito, Philippe Georgel, Marije I Koenders, Mark Boldin, Gernot Schabbauer, Mariola Kurowska-Stolarska, Günter Steiner, Josef S Smolen, Kurt Redlich, Stephan Blüml
Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation...
May 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#3
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28483439/ustekinumab-for-beh%C3%A3-et-s-disease
#4
Adrien Mirouse, Stéphane Barete, Jean-Benoît Monfort, Matthieu Resche-Rigon, Anne-Sophie Bouyer, Cloé Comarmond, Damien Sène, Fanny Domont, Yasmina Ferfar, Patrice Cacoub, David Saadoun
OBJECTIVE: To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behçet's disease (BD). PATIENTS AND METHODS: Prospective study including 14 patients [median age of 39 (34; 41) years, with 71% of men] fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks...
May 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28479213/original-antigenic-sin-a-comprehensive-review
#5
REVIEW
Anup Vatti, Diana M Monsalve, Yovana Pacheco, Christopher Chang, Juan-Manuel Anaya, M Eric Gershwin
The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect...
May 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28479212/innate-lymphoid-cell-derived-cytokines-in-autoimmune-diseases
#6
REVIEW
Sirui Li, Di Yang, Tingwei Peng, Yuzhang Wu, Zhiqiang Tian, Bing Ni
The most recently recognized types of immune cells, the innate lymphoid cells (ILCs), have been sub-divided according to respective distinct expression profiles of regulatory factors or/and cytokines. ILCs have also been shown to participate in a variety of beneficial immune responses, including participation in attack against pathogens and mediation of the pre-inflammatory and inflammatory responses through their production of pro-inflammatory cytokines. As such, while the ILCs exert protective effects they may also become detrimental upon dysregulation...
May 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28476239/defective-il-4-signaling-in-t-cells-defines-severe-common-variable-immunodeficiency
#7
Eli Taraldsrud, Børre Fevang, Silje F Jørgensen, Kristine Moltu, Vera Hilden, Kjetil Taskén, Pål Aukrust, June H Myklebust, Johanna Olweus
Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and B-cell dysfunction, with significant clinical and immunological heterogeneity. Severe non-infectious complications, such as autoimmunity, granulomatous disease and splenomegaly, constitute a major cause of morbidity in CVID patients. T cells are generally regarded important for development of these clinical features. However, while T-cell abnormalities have been found in CVID patients, functional characteristics of T cells corresponding to well-defined clinical subtypes have not been identified...
May 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28465139/diagnostic-potential-of-netosis-derived-products-for-disease-activity-atherosclerosis-and-therapeutic-effectiveness-in-rheumatoid-arthritis-patients
#8
C Pérez-Sánchez, P Ruiz-Limón, M A Aguirre, Y Jiménez-Gómez, I Arias-de la Rosa, M C Ábalos-Aguilera, A Rodriguez-Ariza, M C Castro-Villegas, R Ortega-Castro, P Segui, C Martinez, R Gonzalez-Conejero, S Rodríguez-López, J A Gonzalez-Reyes, J M Villalba, E Collantes-Estévez, A Escudero, N Barbarroja, Ch López-Pedrera
OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker...
April 29, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28461090/nad-dependent-deacetylase-sirtuin-5-rescues-the-innate-inflammatory-response-of-endotoxin-tolerant-macrophages-by-promoting-acetylation-of-p65
#9
Kewei Qin, Chaofeng Han, Hua Zhang, Tianliang Li, Nan Li, Xuetao Cao
The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hyper-inflammation during the acute phase and the hypo-inflammation during immunosuppressive phase of sepsis. However, the mechanisms for controlling hypo-inflammatory response in endotoxin tolerant macrophages remain to be fully understood...
April 28, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28438433/contribution-of-inhibitory-receptor-tigit-to-nk-cell-education
#10
Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans-Gustaf Ljunggren, Wayne M Yokoyama, Zhigang Tian
Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT(+) NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand...
April 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28431796/lessons-learned-from-twins-in-autoimmune-and-chronic-inflammatory-diseases
#11
REVIEW
Elena Generali, Angela Ceribelli, Maria Antonietta Stazi, Carlo Selmi
Autoimmunity and chronic inflammation recognize numerous shared factors and, as a result, the resulting diseases frequently coexist in the same patients or respond to the same treatments. Among the convenient truths of autoimmune and chronic inflammatory diseases, there is now agreement that these are complex conditions in which the individual genetic predisposition provides a rate of heritability. The concordance rates in monozygotic and dizygotic twins allows to estimate the weight of the environment in determining disease susceptibility, despite recent data supporting that only a minority of immune markers depend on hereditary factors...
April 18, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28420548/expression-of-long-non-coding-rnas-in-autoimmunity-and-linkage-to-enhancer-function-and-autoimmune-disease-risk-genetic-variants
#12
T M Aune, P S Crooke, A E Patrick, J T Tossberg, N J Olsen, C F Spurlock
Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders...
April 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28412046/the-epigenetic-mechanism-for-discordance-of-autoimmunity-in-monozygotic-twins
#13
REVIEW
Zhongyuan Xiang, Yuanqing Yang, Christopher Chang, Qianjin Lu
Monozygotic twins share an identical DNA sequence but are not truly "identical". In fact, when it comes to health and disease, they may often display some level of phenotypic discordance. The cause of this discordance is often unknown. Epigenetic modifications such as DNA methylation, histone modification, and microRNAs-mediated regulation regulate gene expression and are sensitive to external stimuli. These modifications may be seen to bridge the gap between genetics and the environment. Over the years, the importance of epigenetics as a primary mechanism for the role that the environment plays in defining phenotype has been increasingly appreciated...
April 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28400082/immune-dysregulation-in-immunodeficiency-disorders-the-role-of-t-cell-receptor-sequencing
#14
REVIEW
Gabriel K Wong, James M Heather, Sara Barmettler, Mark Cobbold
Immune dysregulation is a prominent feature of primary immunodeficiency disorders, which commonly manifested as autoimmunity, cytopenias and inflammatory bowel disease. In partial T-cell immunodeficiency disorders, it has been proposed that the imbalance between effector and regulatory T-cells drives the breakdown of peripheral tolerance. While there is no robust test for immune dysregulation, the T-cell receptor repertoire is used as a surrogate marker, and has been shown to be perturbed in a number of immunodeficiency disorders featuring immune dysregulation including Omenn's Syndrome, Wiskott-Aldrich Syndrome, and common variable immunodeficiency...
April 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28390747/fcrl4-b-cells-in-salivary-glands-of-primary-sj%C3%A3-gren-s-syndrome-patients
#15
Erlin A Haacke, Hendrika Bootsma, Fred K L Spijkervet, Annie Visser, Arjan Vissink, Philip M Kluin, Frans G M Kroese
Fc receptor-like protein 4 (FcRL4) is normally expressed on a small subset of mucosa-associated B-cells, as well as on mucosa-associated lymphoid tissue (MALT) lymphoma B-cells. Primary Sjögren's syndrome (pSS) patients have an increased risk of developing MALT lymphomas, preferentially in the parotid glands. For this reason we studied here by immunohistochemistry and mRNA analysis whether FcRL4 expressing B-cells are present in salivary gland tissue (labial and parotid) of pSS patients (n = 54) and non-pSS sicca patients (n = 16) and whether parotid gland MALT lymphomas in pSS patients (n = 49) also express this receptor...
April 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28389038/mass-cytometry-identifies-a-distinct-monocyte-cytokine-signature-shared-by-clinically-heterogeneous-pediatric-sle-patients
#16
W E O'Gorman, D S Kong, I M Balboni, P Rudra, C R Bolen, D Ghosh, M M Davis, G P Nolan, E W Y Hsieh
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease with heightened disease severity in children. The incomplete understanding of the precise cellular and molecular events that drive disease activity pose a significant hurdle to the development of targeted therapeutic agents. Here, we performed single-cell phenotypic and functional characterization of pediatric SLE patients and healthy controls blood via mass cytometry. We identified a distinct CD14(hi) monocyte cytokine signature, with increased levels of monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein-1β (Mip1β), and interleukin-1 receptor antagonist (IL-1RA)...
April 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28385374/central-immune-tolerance-depends-on-crosstalk-between-the-classical-and-alternative-nf-%C3%AE%C2%BAb-pathways-in-medullary-thymic-epithelial-cells
#17
Marc Riemann, Nico Andreas, Maria Fedoseeva, Elke Meier, Debra Weih, Helga Freytag, Ruth Schmidt-Ullrich, Ulf Klein, Zhao-Qi Wang, Falk Weih
Medullary thymic epithelial cells (mTECs) contribute to self-tolerance by expressing and presenting peripheral tissue antigens for negative selection of autoreactive T cells and differentiation of natural regulatory T cells. The molecular control of mTEC development remains incompletely understood. We here demonstrate by TEC-specific gene manipulation in mice that the NF-κB transcription factor subunit RelB, which is activated by the alternative NF-κB pathway, regulates development of mature mTECs in a dose-dependent manner...
April 3, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28381345/vaccination-recommendations-for-the-adult-immunosuppressed-patient-a-systematic-review-and-comprehensive-field-synopsis
#18
REVIEW
Anthony Lopez, Xavier Mariette, Hervé Bachelez, Alexandre Belot, Bernard Bonnotte, Eric Hachulla, Morad Lahfa, Olivier Lortholary, Pierre Loulergue, Stéphane Paul, Xavier Roblin, Jean Sibilia, Mariela Blum, Silvio Danese, Stefanos Bonovas, Laurent Peyrin-Biroulet
BACKGROUND: Immunosuppressed patients are at risk of severe viral infections-related complications. National and international vaccination guidelines have been developed to decrease the mortality risk associated with these infections. However, a summary of these guidelines and the value of immunisation in this population is missing. OBJECTIVES: To summarize specific guidelines regarding vaccination in immunosuppressed patients. METHODS: We performed a literature search based on last update vaccine guidelines in immunosuppressed adult patients published between 1/1/2005-1/31/2016 in English or French language using PubMed, Cochrane and Embase, as well as relevant medical society websites...
April 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28343748/b-cells-expressing-the-iga-receptor-fcrl4-participate-in-the-autoimmune-response-in-patients-with-rheumatoid-arthritis
#19
Khaled Amara, Elizabeth Clay, Lorraine Yeo, Daniel Ramsköld, Julia Spengler, Natalie Sippl, James A Cameron, Lena Israelsson, Philip J Titcombe, Caroline Grönwall, Ilfita Sahbudin, Andrew Filer, Karim Raza, Vivianne Malmström, Dagmar Scheel-Toellner
The clinical efficacy of B cell targeting therapies highlights the pathogenic potential of B cells in inflammatory diseases. Expression of Fc Receptor like 4 (FcRL4) identifies a memory B cell subset, which is enriched in the joints of patients with rheumatoid arthritis (RA) and in mucosa-associated lymphoid tissue. The high level of RANKL production by this B cell subset indicates a unique pathogenic role. In addition, recent work has identified a role for FcRL4 as an IgA receptor, suggesting a potential function in mucosal immunity...
March 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#20
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 23, 2017: Journal of Autoimmunity
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