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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/28342735/inhibition-of-effector-antigen-specific-t-cells-by-intradermal-administration-of-heme-oxygenase-1-inducers
#1
Thomas Simon, Julien Pogu, Séverine Rémy, Frédéric Brau, Sylvie Pogu, Maud Maquigneau, Jean-François Fonteneau, Nicolas Poirier, Bernard Vanhove, Gilles Blancho, Eliane Piaggio, Ignacio Anegon, Philippe Blancou
Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#2
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 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28330758/regulation-of-type-i-interferon-signaling-in-immunity-and-inflammation-a-comprehensive-review
#3
REVIEW
Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls...
March 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28325644/dnase-active-trex1-frame-shift-mutants-induce-serologic-autoimmunity-in-mice
#4
Tomomi Sakai, Takuya Miyazaki, Dong-Mi Shin, Yong-Soo Kim, Chen-Feng Qi, Robert Fariss, Jeeva Munasinghe, Hongsheng Wang, Alexander L Kovalchuk, Parul H Kothari, Charles S Fermaintt, John P Atkinson, Fred W Perrino, Nan Yan, Herbert C Morse
TREX1/DNASE III, the most abundant 3'-5' DNA exonuclease in mammalian cells, is tail-anchored on the endoplasmic reticulum (ER). Mutations at the N-terminus affecting TREX1 DNase activity are associated with autoimmune and inflammatory conditions such as Aicardi-Goutières syndrome (AGS). Mutations in the C-terminus of TREX1 cause loss of localization to the ER and dysregulation of oligosacchryltransferase (OST) activity, and are associated with retinal vasculopathy with cerebral leukodystrophy (RVCL) and in some cases with systemic lupus erythematosus (SLE)...
March 18, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28325643/alpha-cells-the-main-source-of-il-1%C3%AE-in-human-pancreas
#5
Florence Anquetil, Somayeh Sabouri, Charles Thivolet, Teresa Rodriguez-Calvo, Jose Zapardiel-Gonzalo, Natalie Amirian, Darius Schneider, Ericka Castillo, Yasaman Lajevardi, Matthias G von Herrath
Interleukin-1β (IL-1β) is known to trigger beta cell dysfunction in vitro and could potentially play a role during the pathogenesis of type 1 diabetes and type 2 diabetes. However, several clinical trials attempting to block IL-1β function have had minimal success. We therefore re-investigated local expression of IL-1β in human diabetic and non-diabetic pancreata. We obtained pancreatic tissue sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) including non-diabetic (n = 9), non-diabetic auto-antibody positive (AAb+, n = 5), type 1 diabetes (n = 6), and type 2 diabetes (n = 6) donors...
March 18, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28318807/microrna-302d-targets-irf9-to-regulate-the-ifn-induced-gene-expression-in-sle
#6
Siobhán Smith, Thilini Fernando, Pei Wen Wu, Jane Seo, Joan Ní Gabhann, Olga Piskareva, Eoghan McCarthy, Donough Howard, Paul O'Connell, Richard Conway, Phil Gallagher, Eamonn Molloy, Raymond L Stallings, Grainne Kearns, Lindsy Forbess, Mariko Ishimori, Swamy Venuturupalli, Daniel Wallace, Michael Weisman, Caroline A Jefferies
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs)...
March 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#7
Bergithe E Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R Holdsworth, Christopher N Hahn, Andreas W Schreiber, Hamish S Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs...
March 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28291659/identification-of-carbamylated-alpha-1-anti-trypsin-a1at-as-an-antigenic-target-of-anti-carp-antibodies-in-patients-with-rheumatoid-arthritis
#8
Marije K Verheul, Alvin Yee, Andrea Seaman, George M Janssen, Peter A van Veelen, Jan W Drijfhout, Rene E M Toes, Michael Mahler, Leendert A Trouw
In 2011 a novel autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, was described in rheumatoid arthritis (RA) patients. Anti-CarP antibody positivity associates with a more severe disease course, is observed years before disease onset, and may predict the development of RA in arthralgia patients. Although many clinical observations have been carried out, information on the antigenic targets of anti-CarP antibodies is limited. Most studies on anti-CarP antibodies utilize an ELISA-based assay with carbamylated fetal calf serum (Ca-FCS) as antigen, a complex mixture of proteins...
March 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28285736/nk-cell-subsets-in-autoimmune-diseases
#9
REVIEW
Cai Zhang, Zhigang Tian
Natural killer (NK) cells are lymphocytes of the innate immune system. They not only exert cell-mediated cytotoxicity against tumor cells or infected cells, but also play regulatory role through promoting or suppressing functions of other immune cells by secretion of cytokines and chemokines. However, overactivation or dysfunction of NK cells may be associated with pathogenesis of some diseases. NK cells are found to act as a two edged weapon and play opposite roles with both regulatory and inducer activity in autoimmune diseases...
March 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#10
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28279626/maternal-foetal-outcomes-in-pregnant-women-with-glomerulonephritides-are-all-glomerulonephritides-alike-in-pregnancy
#11
Giorgina Barbara Piccoli, Rossella Attini, Gianfranca Cabiddu, Isabelle Kooij, Federica Fassio, Martina Gerbino, Stefania Maxia, Marilisa Biolcati, Elisabetta Versino, Tullia Todros
In spite of the interest for chronic renal diseases (CKD) in pregnancy data on specific diseases is fragmentary; while recent studies analysed the most common glomerulonephritides (GN), none was addressed at GN as a group. The aim of our study was to analyse the main pregnancy-related outcomes in GN patients in a large multicentre cohort. Patients with a diagnosis of GN were selected from the TOCOS cohort (TOCOS: TOrino Cagliari Observational Study): out of 714 singleton deliveries GN was the diagnosis in 126; lupus GN and IgA nephropathy accounted for 37 and 33 cases; 1418 low-risk singleton deliveries followed-up in the same Centers served as controls (non diabetic, non nephropathic, non obese women, without any other known chronic illness; pregnancies after ovodonation or in vitro fertilisation were excluded, if declared)...
March 6, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28256368/checkpoint-based-immunotherapy-for-autoimmune-diseases-opportunities-and-challenges
#12
EDITORIAL
Xiao-Song He, M Eric Gershwin, Aftab A Ansari
Immune checkpoint pathways modulate the T cell response to ensure their dual function in maintaining health, eradicating or controlling malignancy and infection, as well as tolerating host autoantigens. Dysregulation of the checkpoint pathways may lead to development of cancer or persistent infection, or alternately, autoimmune diseases. Currently available treatments for autoimmune diseases, such as steroid and nonsteroid immunosuppressive medicines, have limited efficacy. Checkpoint-based immunotherapy, designed to directly block the activation pathway or agitate the inhibitory pathway of autoreactive T cells, is a promising therapeutic strategy for restoring T cell tolerance in autoimmune diseases...
February 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28256367/impact-of-systemic-lupus-erythematosus-on-maternal-and-fetal-outcomes-following-pregnancy-a-meta-analysis-of-studies-published-between-years-2001-2016
#13
REVIEW
Pravesh Kumar Bundhun, Mohammad Zafooruddin Sani Soogund, Feng Huang
BACKGROUND: Previous research has already shown systemic lupus erythematosus (SLE) to have severe consequences on pregnancy outcomes. However, insufficient number of participants, which were mainly limited to one particular region, limited outcomes analyzed and lack of evidence based analysis to support systematic reviews of the literature were the limitations observed. Therefore, by improving these limitations, we aimed to systematically show the impact of SLE on maternal and fetal outcomes following pregnancy...
February 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#14
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28238526/mitochondrial-dna-oxidation-induces-imbalanced-activity-of-nlrp3-nlrp6-inflammasomes-by-activation-of-caspase-8-and-brcc36-in-dry-eye
#15
Wei Chi, Xia Hua, Xin Chen, Fang Bian, Xiaoyong Yuan, Lili Zhang, Xiaoran Wang, Ding Chen, Ruzhi Deng, Zhijie Li, Yizhi Liu, Cintia S de Paiva, Stephen C Pflugfelder, De-Quan Li
The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#16
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28214146/impact-of-anti-tnf-therapy-on-nk-cells-function-and-on-immunosurveillance-against-b-cell-lymphomas
#17
Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Juliette Pascaud, Audrey Paoletti, Xavier Mariette
OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of lymphoma linked to activity of the disease. Immunosuppressive drugs have been suspected to induce an additional risk. Since, NK cells have been recently shown to participate to anti-lymphoma immunosurveillance, we aimed to assess if anti-TNF might impact their anti-lymphoma activity. METHODS: NK cells have been assessed ex vivo in patients with RA treated with methotrexate (MTX) with or without anti-TNF...
February 14, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28209290/efficacy-safety-and-pharmacokinetics-of-biosimilars-of-anti-tumor-necrosis-factor-%C3%AE-agents-in-rheumatic-diseases-a-systematic-review-and-meta-analysis
#18
REVIEW
Yuga Komaki, Akihiro Yamada, Fukiko Komaki, Praneeth Kudaravalli, Dejan Micic, Akio Ido, Atsushi Sakuraba
OBJECTIVE: To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents...
February 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28196704/toll-like-receptor-4-antagonist-tak-242-inhibits-autoinflammatory-symptoms-in-ditra
#19
Akitaka Shibata, Kazumitsu Sugiura, Yasuhide Furuta, Yoshiko Mukumoto, Osamu Kaminuma, Masashi Akiyama
BACKGROUND: IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), and loss-of-function mutations in IL36RN define a recessively inherited autoinflammatory disease named "deficiency of IL-36Ra" (DITRA). DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy...
February 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28190705/risk-of-autoimmune-diseases-and-human-papilloma-virus-hpv-vaccines-six-years-of-case-referent-surveillance
#20
Lamiae Grimaldi-Bensouda, Michel Rossignol, Isabelle Koné-Paut, Alain Krivitzky, Christine Lebrun-Frenay, Johanna Clet, David Brassat, Caroline Papeix, Marc Nicolino, Pierre-Yves Benhamou, Olivier Fain, Nathalie Costedoat-Chalumeau, Marie-France Courcoux, Jean-François Viallard, Bertrand Godeau, Thomas Papo, Patrick Vermersch, Isabelle Bourgault-Villada, Gerard Breart, Lucien Abenhaim
BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]...
February 9, 2017: Journal of Autoimmunity
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