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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/28089248/triggering-receptor-expressed-on-myeloid-cells-1-trem-1-deficiency-augments-baff-production-to-promote-lupus-progression
#1
Chi-Jui Liu, Chang-Youh Tsai, Ssu-Hsuan Chiang, Shye-Jye Tang, Nien-Jung Chen, Tak Wah Mak, Guang-Huan Sun, Kuang-Hui Sun
Sensing of nucleic acids by pattern recognition receptors is the key for the initiation and development of systemic lupus erythematosus (SLE). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a novel innate immune receptor, which can amplify Toll-like receptor (TLR)-induced inflammatory responses. Although patients with lupus exhibit increased serum levels of soluble TREM-1 (sTREM-1), the role of TREM-1 in SLE remains unknown. In current study, we found serum sTREM-1 levels were significantly increased in lupus patients and positively correlated with disease activity...
January 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28082047/smoking-activates-cytotoxic-cd8-t-cells-and-causes-survivin-release-in-rheumatoid-arthritis
#2
Caroline Wasén, Minna Turkkila, Apostolos Bossios, Malin Erlandsson, Karin M Andersson, Linda Ekerljung, Carina Malmhäll, Mikael Brisslert, Sofia Töyrä Silfverswärd, Bo Lundbäck, Maria I Bokarewa
CD8(+) T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of CD8(+) T cells, defined by lost function of PD-1, and development of arthritis. We investigated how smoking contributes to the non-exhausted phenotype of CD8(+) T cells and cause survivin release to serum. We compared serum survivin levels between smokers and non-smokers in 252 RA and 168 healthy subjects. Nicotine effects on CD8(+) T cells were studied in peripheral blood of smoking women, bone marrow of nicotine treated mice and in sorted CD8 spleen cells in vitro using flow cytometry and quantitative PCR...
January 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28082046/a-comprehensive-evaluation-for-the-treatment-of-lupus-nephritis
#3
REVIEW
Evangelia Zampeli, Dennis M Klinman, M Eric Gershwin, Haralampos M Moutsopoulos
Systemic lupus is the prototypic human autoimmune disease. It is a kaleidoscope of autoreactivities, with clear indications of both a genetic and environmental basis. Indeed, it is a disease that can manifest in virtually every tissue and organ and can also be found spontaneously in a number of animal species, including dogs, cats and horses. Moreover, there are multiple murine models of lupus, the first of which, New Zealand Black (NZB) mice, were discovered in 1959. Despite an enormous effort from scientists in multiple disciplines, the etiology of lupus remains elusive and the introduction of new therapies has been disappointing...
January 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28063629/the-autoimmune-risk-gene-zmiz1-is-a-vitamin-d-responsive-marker-of-a-molecular-phenotype-of-multiple-sclerosis
#4
N L Fewings, P N Gatt, F C McKay, G P Parnell, S D Schibeci, J Edwards, M A Basuki, A Goldinger, M J Fabis-Pedrini, A G Kermode, C P Manrique, J L McCauley, D Nickles, S E Baranzini, T Burke, S Vucic, G J Stewart, D R Booth
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28063628/separate-effects-of-the-ankylosing-spondylitis-associated-erap1-and-erap2-aminopeptidases-determine-the-influence-of-their-combined-phenotype-on-the-hla-b-27-peptidome
#5
Adrian Martín-Esteban, Alejandro Sanz-Bravo, Pablo Guasp, Eilon Barnea, Arie Admon, José A López de Castro
Ankylosing spondylitis (AS) is an inflammatory disease strongly associated with the Major Histocompatibility Complex class I (MHC-I) allotype HLA-B*27. The endoplasmic reticulum aminopeptidases (ERAP)1 and 2, which trim peptides to their optimal length for MHC-I binding, are also susceptibility factors for this disease. Both highly active ERAP1 variants and ERAP2 expression favor AS, whereas loss-of-function ERAP1 and loss-of-expression ERAP2 variants are protective. Yet, only ERAP1 is in epistasis with HLA-B*27...
January 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28062188/a-comprehensive-analysis-and-immunobiology-of-autoimmune-neurological-syndromes-during-the-zika-virus-outbreak-in-c%C3%A3%C2%BAcuta-colombia
#6
Juan-Manuel Anaya, Yhojan Rodríguez, Diana M Monsalve, Daniel Vega, Ernesto Ojeda, Diana González-Bravo, Mónica Rodríguez-Jiménez, Carlos A Pinto-Díaz, Pablo Chaparro, María L Gunturiz, Aftab A Ansari, M Eric Gershwin, Nicolás Molano-González, Carolina Ramírez-Santana, Yeny Acosta-Ampudia
We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed...
January 3, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28040323/environmental-factor-and-inflammation-driven-alteration-of-the-total-peripheral-t-cell-compartment-in-granulomatosis-with-polyangiitis
#7
Anja Kerstein, Silke Schüler, Otávio Cabral-Marques, Juliane Fazio, Robert Häsler, Antje Müller, Silke Pitann, Frank Moosig, Sebastian Klapa, Christian Haas, Dieter Kabelitz, Gabriela Riemekasten, Steffen Wolters, Peter Lamprecht
Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far. In granulomatosis with polyangiitis (GPA), a prototypical autoimmune disorder of unknown aetiology, we performed for the first time a combined approach using phenotyping, transcriptome and functional analyses of T-cell populations to evaluate triggers of memory T-cell expansion...
December 28, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28012697/the-host-defense-peptide-ll-37-a-possible-inducer-of-the-type-i-interferon-system-in-patients-with-polymyositis-and-dermatomyositis
#8
Xin Lu, Quan Tang, Monica Lindh, Maryam Dastmalchi, Helene Alexanderson, Karin Popovic Silwerfeldt, Birgitta Agerberth, Ingrid E Lundberg, Cecilia Wick
The type I interferon (IFN) system has recently been suggested to play important and essential roles in the pathogenesis of myositis. However, a clarification of how type I IFNs could function as triggering factor(s) in the pathogenesis of myositis has yet failed. Through activation of the type I IFN system, the host defense peptide LL-37 carries numerous immunomodulatory properties and is implicated in the pathogenesis of several other autoimmune diseases, including systemic lupus erythematosus (SLE). The expression of LL-37 can be regulated by various endogenous factors including the active form of vitamin D (25(OH)D3)...
December 22, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27974250/the-influence-of-genetic-predisposition-and-autoimmune-hepatitis-inducing-antigens-in-disease-development
#9
Matthias Hardtke-Wolenski, Janine Dywicki, Katja Fischer, Martin Hapke, Maren Sievers, Jerome Schlue, Mark S Anderson, Richard Taubert, Fatih Noyan, Michael P Manns, Elmar Jäckel
: Autoimmune hepatitis (AIH) is defined as a chronic liver inflammation with loss of tolerance against hepatocytes. The etiology and pathophysiology of AIH are still poorly understood because reliable animal models are limited. Therefore, we recently introduced a model of experimental murine AIH by a self-limited adenoviral infection with the AIH type 2 antigen formiminotransferase cyclodeaminase (FTCD). We could demonstrate that break of humoral tolerance towards liver specific autoantigens like FTCD and cytochrome P450 2D6 (CYP2D6) is not dependent on the genetic background...
December 11, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27965060/igg4-autoantibodies-against-muscle-specific-kinase-undergo-fab-arm-exchange-in-myasthenia-gravis-patients
#10
Inga Koneczny, Jo A A Stevens, Anna De Rosa, Saif Huda, Maartje G Huijbers, Abhishek Saxena, Michelangelo Maestri, Konstantinos Lazaridis, Paraskevi Zisimopoulou, Socrates Tzartos, Jan Verschuuren, Silvère M van der Maarel, Philip van Damme, Marc H De Baets, Peter C Molenaar, Angela Vincent, Roberta Ricciardi, Pilar Martinez-Martinez, Mario Losen
Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission...
December 10, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27965059/epigenetics-of-psoriatic-disease-a-systematic-review-and-critical-appraisal
#11
Remy A Pollock, Fatima Abji, Dafna D Gladman
Psoriasis is an inflammatory disease of the skin that is sometimes accompanied by an auto-inflammatory arthritis called psoriatic arthritis (PsA). Psoriasis and PsA are multifactorial diseases that result from complex interactions of environmental and genetic risk factors. Epigenetic marks, which are labile chemical marks with diverse functions, form a layer of biological information that sits at the interface of genetics and the environment. Aberrant epigenetic regulation has been previously implicated in other rheumatological disorders...
December 10, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27939129/guillain-barr%C3%A3-syndrome-is-induced-in-non-obese-diabetic-nod-mice-following-campylobacter-jejuni-infection-and-is-exacerbated-by-antibiotics
#12
J L St Charles, J A Bell, B J Gadsden, A Malik, H Cooke, L K Van de Grift, H Y Kim, E J Smith, L S Mansfield
Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues...
December 8, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27919567/splicing-factor-proline-glutamine-rich-is-a-novel-autoantigen-of-dermatomyositis-and-associated-with-anti-melanoma-differentiation-associated-gene-5-antibody
#13
Yuji Hosono, Ran Nakashima, Satoshi Serada, Kosaku Murakami, Yoshitaka Imura, Hajime Yoshifuji, Koichiro Ohmura, Tetsuji Naka, Tsuneyo Mimori
OBJECTIVE: Anti-MDA5 antibody positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop into rapidly progressive interstitial lung disease, but their pathogenesis remains unclear. We observed that sera from DM/CADM patients immunoprecipitated a common 110 kDa polypeptide. We investigated this autoantigen and its clinical significance. METHODS: Autoantibodies were screened in 333 patients with various connective tissue diseases (CTDs) and 20 healthy controls (HCs) by immunoprecipitation with [(35)S]methionine-labeled HeLa cells...
December 2, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27899224/interleukin-7-and-15-maintain-pathogenic-memory-th17-cells-in-autoimmunity
#14
Yihe Chen, Sunil K Chauhan, Xuhua Tan, Reza Dana
Th17 cells are principal mediators of many autoimmune conditions. Recently, memory Th17 cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17 cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17 cells. Neutralization of these cytokines leads to substantial reduction of memory Th17 cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt...
November 26, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27894837/cd4-virtual-memory-antigen-inexperienced-t-cells-reside-in-the-na%C3%A3-ve-regulatory-and-memory-t-cell-compartments-at-similar-frequencies-implications-for-autoimmunity
#15
Alina I Marusina, Yoko Ono, Alexander A Merleev, Michiko Shimoda, Hiromi Ogawa, Elizabeth A Wang, Kayo Kondo, Laura Olney, Guillaume Luxardi, Yoshinori Miyamura, Tilahun D Yilma, Itzel Bustos Villalobos, Jennifer W Bergstrom, Daniel G Kronenberg, Athena M Soulika, Iannis E Adamopoulos, Emanual Maverakis
It is widely accepted that central and effector memory CD4(+) T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts...
November 25, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27863820/b-cell-depleting-therapy-regulates-splenic-and-circulating-t-follicular-helper-cells-in-immune-thrombocytopenia
#16
Sylvain Audia, Marzia Rossato, Malika Trad, Maxime Samson, Kim Santegoets, Alexandrine Gautheron, Cornelis Bekker, Olivier Facy, Nicolas Cheynel, Pablo Ortega-Deballon, Mathieu Boulin, Sabine Berthier, Vanessa Leguy-Seguin, Laurent Martin, Marion Ciudad, Nona Janikashvili, Philippe Saas, Timothy Radstake, Bernard Bonnotte
B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet...
November 15, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27829535/a-critical-role-of-transcription-factor-yy1-in-rheumatoid-arthritis-by-regulation-of-interleukin-6
#17
Jinpiao Lin, Yujue He, Junmin Chen, Zhiyong Zeng, Bin Yang, Qishui Ou
Previous studies have revealed a critical role of YY1, a "Yin Yang" transcription factor, in cancer development and progression. However, whether YY1 has any role in rheumatoid arthritis (RA) remains unknown. This study aims to explore the potential role of YY1 in RA pathogenesis. In this study, we found that YY1 was over-expressed in RA patients and CIA mice. Blocking of YY1 action with YY1 shRNA lentivirus ameliorated disease progression in CIA mice. We further analyzed the signaling pathway involved by ingenuity pathway analysis (IPA), results showed IL-6 signaling and JAK/Stat signaling pathway was significantly inhibited by LV-YY1-shRNA treatment...
November 6, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27802879/an-insulin-iapp-hybrid-peptide-is-an-endogenous-antigen-for-cd4-t-cells-in-the-non-obese-diabetic-mouse
#18
Timothy A Wiles, Thomas Delong, Rocky L Baker, Brenda Bradley, Gene Barbour, Roger L Powell, Nichole Reisdorph, Kathryn Haskins
BDC-6.9, a diabetogenic CD4 T cell clone isolated from a non-obese diabetic (NOD) mouse, responds to pancreatic islet cells from NOD but not BALB/c mice. We recently reported that a hybrid insulin peptide (HIP), 6.9HIP, formed by linkage of an insulin C-peptide fragment and a fragment of islet amyloid polypeptide (IAPP), is the antigen for BDC-6.9. We report here that the core 12-mer peptide from 6.9HIP, centered on the hybrid peptide junction, is also highly antigenic for BDC-6.9. In agreement with the observation that BALB/c islet cells fail to stimulate the T cell clone, a single amino acid difference in the BALB/c IAPP sequence renders the BALB/c version of the HIP only weakly antigenic...
October 29, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27793425/impact-of-tofacitinib-treatment-on-human-b-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#19
Marta Rizzi, Raquel Lorenzetti, Kathleen Fischer, Julian Staniek, Iga Janowska, Arianna Troilo, Valentina Strohmeier, Miriam Erlacher, Mirjam Kunze, Bettina Bannert, Diego Kyburz, Reinhard E Voll, Nils Venhoff, Jens Thiel
B-cells are pivotal to the pathogenesis of rheumatoid arthritis and tofacitinib, a JAK inhibitor, is effective and safe in its treatment. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain. Despite extensive data on T-lymphocytes, the impact of tofacitinib on B-lymphocytes is poorly understood. In this study we assessed the effect of tofacitinib on B-lymphocyte differentiation and function. Tofacitinib treatment strongly impaired in vitro plasmablast development, immunoglobulin secretion and induction of B-cell fate determining transcription factors, Blimp-1, Xbp-1, and IRF-4, in naïve B-cells...
October 26, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27784538/phenotyping-and-auto-antibody-production-by-liver-infiltrating-b-cells-in-primary-sclerosing-cholangitis-and-primary-biliary-cholangitis
#20
Brian K Chung, Bardia T Guevel, Gary M Reynolds, D B R K Gupta Udatha, Eva Kristine Klemsdal Henriksen, Zania Stamataki, Gideon M Hirschfield, Tom Hemming Karlsen, Evaggelia Liaskou
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies...
October 24, 2016: Journal of Autoimmunity
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