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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/29146547/a-gene-module-associated-with-dysregulated-tcr-signaling-pathways-in-cd4-t-cell-subsets-in-rheumatoid-arthritis
#1
Shuji Sumitomo, Yasuo Nagafuchi, Yumi Tsuchida, Haruka Tsuchiya, Mineto Ota, Kazuyoshi Ishigaki, Shinichiro Nakachi, Rika Kato, Keiichi Sakurai, Norio Hanata, Shoko Tateishi, Hiroko Kanda, Akari Suzuki, Yuta Kochi, Keishi Fujio, Kazuhiko Yamamoto
We analyzed the transcriptome of detailed CD4(+) T cell subsets including them after abatacept treatment, and examined the difference among CD4(+) T cell subsets and identified gene sets that are closely associated disease activity and abatacept treatment. Seven CD4(+) T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh and Treg) were sorted from PBMCs taken from 10 RA patients and 10 healthy controls, and three RA patients donated samples before and 6 months after abatacept treatment. Paired-end RNA sequencing was performed using HiSeq 2500...
November 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29146546/signaling-via-toll-like-receptor-4-and-cd40-in-b-cells-plays-a-regulatory-role-in-the-pathogenesis-of-multiple-sclerosis-through-interleukin-10-production
#2
Yoichiro Okada, Hirofumi Ochi, Chihiro Fujii, Yuichiro Hashi, Mio Hamatani, Shinji Ashida, Kazuyuki Kawamura, Hirofumi Kusaka, Sadayuki Matsumoto, Masanori Nakagawa, Toshiki Mizuno, Ryosuke Takahashi, Takayuki Kondo
BACKGROUND: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process. OBJECTIVE: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation. METHODS: Peripheral blood mononuclear cells obtained from 34 MS patients and 24 matched healthy participants (HS) were stimulated through either TLR4 or TLR9 alone, or together with CD40...
November 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29129473/dominant-negative-loss-of-function-arises-from-a-second-more-frequent-variant-within-the-sand-domain-of-autoimmune-regulator-aire
#3
Jordan K Abbott, Yu-San Huoh, Paul R Reynolds, Liping Yu, Marian Rewers, Monica Reddy, Mark S Anderson, Sun Hur, Erwin W Gelfand
A genetic variant in the SAND domain of autoimmune regulator (AIRE), R247C, was identified in a patient with type I diabetes mellitus (T1DM) and his mother with rheumatoid arthritis. In vitro, the variant dominantly inhibited AIRE; however, typical features of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECED) were not seen in the subjects. Rather, early manifestation of autoimmunity appeared to be dependent on additional genetic factors. On a population level, diverse variants were identified in this region...
November 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29126851/ccr6-signaling-inhibits-suppressor-function-of-induced-treg-during-gut-inflammation
#4
Neeraja Kulkarni, Heikrujam Thoihen Meitei, Sandip Ashok Sonar, Praveen Kumar Sharma, Vikkarasan Rehman Mujeeb, Sharad Srivastava, Ramanamurthy Boppana, Girdhari Lal
CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3(+)CD4(+) T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6(+) Tregs enhanced the expression of RORγt. The peripheral blood mononuclear cells (PBMCs) of ulcerative colitis (UC) patients showed lower percentages of Foxp3(+)CD4(+) T cells, as compared to healthy individuals, with CCR6(+) Tregs showing higher RORγt expression as compared to CCR6(-)Tregs...
November 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29108670/autophagy-dysfunction-in-autoinflammatory-diseases
#5
REVIEW
Yichao Hua, Min Shen, Christine McDonald, Qingping Yao
Autoinflammatory diseases (AUIDs) are a genetically heterogeneous group of rheumatic diseases characterized by episodic inflammation linked with dysregulated innate immune responses. In this review, we summarize the molecular mechanisms altered by disease-associated variants in several AUIDs, including NOD2-associated diseases, TNF receptor-associated periodic syndrome (TRAPS), familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), and highlight the roles dysregulated autophagy plays in disease pathogenesis...
November 3, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29103803/cd39-and-cd73-activity-are-protective-in-a-mouse-model-of-antiphospholipid-antibody-induced-miscarriages
#6
Anushka N Samudra, Karen M Dwyer, Carly Selan, Susanna Freddi, Lisa Murray-Segal, Mandana Nikpour, Michael J Hickey, Karlheinz Peter, Simon C Robson, Maithili Sashindranath, Peter J Cowan, Harshal H Nandurkar
OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder of young adults associated with devastating pregnancy complications (recurrent miscarriages, preeclampsia and low birth weight) and vascular complications including thrombosis. The key components implicated in pathogenesis of APS are the complement cascade and tissue factor (TF) activity causing inflammation and coagulation. Purinergic signalling involving catabolism of ATP to adenosine by cell-surface enzymes CD39 and CD73 has anti-inflammatory and anti-thrombotic effects...
November 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29100671/-nettling-the-host-breaking-of-tolerance-in-chronic-inflammation-and-chronic-infection
#7
REVIEW
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29079064/wandering-pathways-in-the-regulation-of-innate-immunity-and-inflammation
#8
REVIEW
Alberto Mantovani
Tumor-associated macrophages (TAM) have served as a paradigm of cancer-related inflammation. Moreover, investigations on TAM have led to the dissection of macrophage plasticity and polarization and to the discovery and analysis of molecular pathways of innate immunity, in particular cytokines, chemokines and PTX3 as a prototypic fluid phase pattern recognition molecule. Mechanisms of negative regulation are complex and include decoy receptors, receptor antagonists, anti-inflammatory cytokines and the signalling regulator IL-1R8...
October 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29074164/defective-regulation-of-l1-endogenous-retroelements-in-primary-sjogren-s-syndrome-and-systemic-lupus-erythematosus-role-of-methylating-enzymes
#9
Clio P Mavragani, Adrianos Nezos, Irina Sagalovskiy, Surya Seshan, Kyriakos A Kirou, Mary K Crow
OBJECTIVE: To investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively...
October 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29066221/decreased-sensitivity-to-1-25-dihydroxyvitamin-d3-in-t-cells-from-the-rheumatoid-joint
#10
Louisa E Jeffery, Peter Henley, Nefisa Marium, Andrew Filer, David M Sansom, Martin Hewison, Karim Raza
1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects, including suppression of IL-17 + and IFNγ+ T cells implicated in rheumatoid arthritis (RA), but efficacy at the site of active disease is unclear. To investigate this, T cells from synovial fluid (SF) and paired blood of patients with active RA were studied. 1,25(OH)2D3 had significantly less suppressive effect on Th17 cells (IL-17+IFNγ-) and Th17.1 cells (IL-17+IFNγ+) from SF compared to those from blood, and had no effect on SF CD4(+) or CD8(+) IFNγ+ T cell frequencies...
October 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29066027/interferon-beta-specific-t-cells-are-associated-with-the-development-of-neutralizing-antibodies-in-interferon-beta-treated-multiple-sclerosis-patients
#11
Sudhakar Reddy Kalluri, Verena Grummel, Zsuzsanna Hracsko, Viola Pongratz, Verena Pernpeintner, Christiane Gasperi, Dorothea Buck, Bernhard Hemmer
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29066026/cd4-cd28-kir-cd11a-hi-t-cells-correlate-with-disease-activity-and-are-characterized-by-a-pro-inflammatory-epigenetic-and-transcriptional-profile-in-lupus-patients
#12
Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M Strickland, Nathan C Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D Wren, Pei-Suen Tsou, Emily E Lewis, Kathleen Maksimowicz-McKinnon, W Joseph McCune, Bruce C Richardson, Amr H Sawalha
OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus. METHODS: The size of the CD4+CD28+KIR+CD11a(hi) T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a(hi) T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29056249/nephrutix-a-randomized-double-blind-placebo-vs-rituximab-controlled-trial-assessing-t-cell-subset-changes-in-minimal-change-nephrotic-syndrome
#13
Ahmed Boumediene, Pauline Vachin, Kelhia Sendeyo, Julie Oniszczuk, Shao-Yu Zhang, Carole Henique-Greciet, Andre Pawlak, Vincent Audard, Mario Ollero, Vincent Guigonis, Djillali Sahali
Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular disease. We have analyzed the modifications on T-cell subsets in twenty-three patients who were highly steroid/calcineurin inhibitor and/or mycophenolate mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab-controlled trial. Patients with FRNS entered the trial at remission and were randomly assigned to receive either Rituximab or placebo...
October 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29054368/an-intermediate-level-of-cd161-expression-defines-a-novel-activated-inflammatory-and-pathogenic-subset-of-cd8-t-cells-involved-in-multiple-sclerosis
#14
Bryan Nicol, Marion Salou, Isabel Vogel, Alexandra Garcia, Emilie Dugast, Jeremy Morille, Stéphanie Kilens, Eric Charpentier, Audrey Donnart, Steven Nedellec, Marylène Jacq-Foucher, Fabienne Le Frère, Sandrine Wiertlewski, Arnaud Bourreille, Sophie Brouard, Laure Michel, Laurent David, Pierre-Antoine Gourraud, Nicolas Degauque, Arnaud B Nicot, Laureline Berthelot, David-Axel Laplaud
Several lines of evidence support a key role for CD8(+) T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8(+) T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date...
October 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29037440/novel-genetic-loci-associated-hla-b-08-01-positive-myasthenia-gravis
#15
Jezabel Varade, Ning Wang, Che Kang Lim, Tao Zhang, Yuanwei Zhang, Xiaomin Liu, Fredrik Piehl, Ritva Matell, Hongzhi Cao, Xun Xu, Lennart Hammarström
OBJECTIVE: To identify potential causative markers involved in the development of early-onset myasthenia gravis (EOMG) in the MHC and non-MHC regions that may interact with the HLA-B*08:01 allele. METHODS: We analyzed 583 MG patients and identified 5 patients homozygous for the disease-associated ancestral haplotype 8.1 (HLA-A*01:01, B*08:01, DRB1*03:01, DQB1*02:01). We also analyzed more than 9000 controls and selected 24 for further investigation. We subsequently conducted a fine mapping analysis through high-throughput sequencing of the MHC region (from upstream of the GPα5 gene to downstream of the ZBTB9 gene)...
October 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29033144/impaired-anti-inflammatory-activity-of-ppar%C3%AE-in-the-salivary-epithelia-of-sj%C3%A3-gren-s-syndrome-patients-imposed-by-intrinsic-nf-%C3%AE%C2%BAb-activation
#16
Aigli G Vakrakou, Alexandros Polyzos, Efstathia K Kapsogeorgou, Dimitris Thanos, Menelaos N Manoussakis
Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important anti-inflammatory activities in epithelial cells. Herein, the comparative analysis of SG biopsies and SGEC lines obtained from SS patients and controls had revealed constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function in the ductal epithelia of SS patients that were associated with cell-autonomously activated NF-κB and IL-1β pathways...
October 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28988642/risk-of-beta-cell-autoimmunity-presence-for-progression-to-type-1-diabetes-a-systematic-review-and-meta-analysis
#17
REVIEW
Qing Ling, Jing Lu, Jingjing Li, Qianyue Xu, Dalong Zhu, Yan Bi
BACKGROUND: Islet autoantibodies have been applied for diagnosis of type 1 diabetes mellitus (T1DM) at an asymptomatic stage in individuals with high-risk genotypes. Evidence is insufficient to support a broad application of islet autoantibody screening for T1DM in clinical practice. The aim of this study was to assess the evidence of an association between islet autoantibodies and the development of T1DM in a pooled population of both genetically at-risk individuals and general people without definite genetic background...
October 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28969936/the-dna-methylation-landscape-of-cd4-t-cells-in-oligoarticular-juvenile-idiopathic-arthritis
#18
Raul A Chavez-Valencia, Rachel C Chiaroni-Clarke, David J Martino, Jane E Munro, Roger C Allen, Jonathan D Akikusa, Anne-Louise Ponsonby, Jeffrey M Craig, Richard Saffery, Justine A Ellis
Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4(+) T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illumina HumanMethylation450 arrays...
September 29, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28964723/myelin-oligodendrocyte-glycoprotein-specific-antibodies-from-multiple-sclerosis-patients-exacerbate-disease-in-a-humanized-mouse-model
#19
Priyanka Khare, Dilip K Challa, Siva Charan Devanaboyina, Ramraj Velmurugan, Samuel Hughes, Benjamin M Greenberg, Raimund J Ober, E Sally Ward
Myelin oligodendrocyte glycoprotein (MOG) is exposed on the outer surface of the myelin sheath, and as such, represents a possible target antigen for antibodies in multiple sclerosis (MS) and other demyelinating diseases. However, despite extensive analyses, whether MOG-specific antibodies contribute to pathogenesis in human MS remains an area of uncertainty. In the current study we demonstrate that antibodies derived from adult MS patients exacerbate experimental autoimmune encephalomyelitis (EAE) in 'humanized' mice that transgenically express human FcγRs (hFcγRs)...
September 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28964722/a-t-cell-specific-deletion-of-hdac1-protects-against-experimental-autoimmune-encephalomyelitis
#20
Lisa Göschl, Teresa Preglej, Patricia Hamminger, Michael Bonelli, Liisa Andersen, Nicole Boucheron, Alexandra F Gülich, Lena Müller, Victoria Saferding, Ilgiz A Mufazalov, Kiyoshi Hirahara, Christian Seiser, Patrick Matthias, Thomas Penz, Michael Schuster, Christoph Bock, Ari Waisman, Günter Steiner, Wilfried Ellmeier
Multiple sclerosis (MS) is a human neurodegenerative disease characterized by the invasion of autoreactive T cells from the periphery into the CNS. Application of pan-histone deacetylase inhibitors (HDACi) ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model for MS, suggesting that HDACi might be a potential therapeutic strategy for MS. However, the function of individual HDAC members in the pathogenesis of EAE is not known. In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4(+) T cells to differentiate into Th17 cells...
September 27, 2017: Journal of Autoimmunity
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