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https://www.readbyqxmd.com/read/27924021/aagatlas-1-0-a-human-autoantigen-database
#1
Dan Wang, Liuhui Yang, Ping Zhang, Joshua LaBaer, Henning Hermjakob, Dong Li, Xiaobo Yu
Autoantibodies refer to antibodies that target self-antigens, which can play pivotal roles in maintaining homeostasis, distinguishing normal from tumor tissue and trigger autoimmune diseases. In the last three decades, tremendous efforts have been devoted to elucidate the generation, evolution and functions of autoantibodies, as well as their target autoantigens. However, reports of these countless previously identified autoantigens are randomly dispersed in the literature. Here, we constructed an AAgAtlas database 1...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27922498/inclusion-body-myositis
#2
Steven A Greenberg
PURPOSE OF REVIEW: Inclusion body myositis (IBM) is an enigmatic progressive disease of skeletal muscle. This review provides a summary of the clinical and pathophysiologic aspects of IBM. RECENT FINDINGS: The development of diagnostic blood testing for IBM followed from the discovery of a B-cell pathway in IBM muscle and circulating autoantibodies against NT5C1A, further establishing IBM's status as an autoimmune disease. The key role of cytotoxic T cells in IBM is further supported by the identification of a link between IBM and T-cell large granular lymphocytic leukemia...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27921425/-oxldl-%C3%AE-2-glycoprotein-i-complex-as-a-pro-atherogenic-autoantigen-is-atherosclerosis-an-autoimmune-disease
#3
Pavel Kraml
Oxidation of atherogenic low-density lipoproteins (LDL) plays a key role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interrelated and they can potentiate one another. In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma β2-glycoprotein I (β2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921237/structure-and-activation-of-the-tsh-receptor-transmembrane-domain
#4
Ricardo Núñez Miguel, Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
PURPOSE: The thyroid-stimulating hormone receptor (TSHR) is the target autoantigen for TSHR-stimulating autoantibodies in Graves' disease. The TSHR is composed of: a leucine-rich repeat domain (LRD), a hinge region or cleavage domain (CD) and a transmembrane domain (TMD). The binding arrangements between the TSHR LRD and the thyroid-stimulating autoantibody M22 or TSH have become available from the crystal structure of the TSHR LRD-M22 complex and a comparative model of the TSHR LRD in complex with TSH, respectively...
December 2017: Auto- Immunity Highlights
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
#5
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/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#6
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27909160/evaluation-of-polymorphic-variants-in-apoptotic-genes-and-their-role-in-susceptibility-and-clinical-progression-to-systemic-lupus-erythematosus
#7
N Glesse, P Vianna, L M G Paim, M C C Matte, A K K Aguiar, P L Palhano, O A Monticielo, C V Brenol, R M Xavier, J A B Chies
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes...
November 30, 2016: Lupus
https://www.readbyqxmd.com/read/27906045/smoking-is-associated-with-the-concurrent-presence-of-multiple-autoantibodies-in-rheumatoid-arthritis-rather-than-with-anti-citrullinated-protein-antibodies-per-se-a-multicenter-cohort-study
#8
Tineke J van Wesemael, Sofia Ajeganova, Jennifer Humphreys, Chikashi Terao, Ammar Muhammad, Deborah P M Symmons, Alex J MacGregor, Ingiäld Hafström, Leendert A Trouw, Annette H M van der Helm-van Mil, Tom W J Huizinga, Tsuneyo Mimori, René E M Toes, Fumihiko Matsuda, Björn Svensson, Suzanne M M Verstappen, Diane van der Woude
BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27903713/-trained-immunity-consequences-for-lymphoid-malignancies
#9
REVIEW
Wendy B C Stevens, Mihai G Netea, Arnon P Kater, Walter J F M van der Velden
In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27899808/autoimmunity-to-hsp60-during-diet-induced-obesity-in-mice
#10
M E Şelli, G Wick, D C Wraith, A C Newby
Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60...
November 30, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27895639/netosis-as-source-of-autoantigens-in-rheumatoid-arthritis
#11
REVIEW
Elisa Corsiero, Federico Pratesi, Edoardo Prediletto, Michele Bombardieri, Paola Migliorini
In neutrophils (but also in eosinophils and in mast cells), different inflammatory stimuli induce histone deimination, chromatin decondensation, and NET formation. These web-like structures that trap and kill microbes contain DNA, cationic granule proteins, and antimicrobial peptides, but the most abundant proteins are core histones. Histones contained in NETs have been deiminated, and arginines are converted in citrullines. While deimination is a physiological process amplified in inflammatory conditions, only individuals carrying genetic predisposition to develop rheumatoid arthritis (RA) make antibodies to deiminated proteins...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888685/label-free-piezoelectric-biosensor-for-prognosis-and-diagnosis-of-systemic-lupus-erythematosus
#12
Noelle M do Nascimento, Augusto Juste-Dolz, Elena Grau-García, Jose A Román-Ivorra, Rosa Puchades, Angel Maquieira, Sergi Morais, David Gimenez-Romero
An autoantigen piezoelectric sensor to quantify specific circulating autoantibodies in human serum is developed. The sensor consisted on a quartz crystal microbalance with dissipation monitoring (QCM-D) where TRIM21 and TROVE2 autoantigens were covalently immobilized, allowing the selective determination of autoantibodies for diagnosis and prognosis of Systemic Lupus Erythematosus (SLE). The sensitivity of the biosensor, measured as IC50 value, was 1.51U/mL and 0.32U/mL, for anti-TRIM21 and anti-TROVE2 circulating autoantibodies, respectively...
November 9, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27886238/mc5r-and-a2ar-deficiencies-during-experimental-autoimmune-uveitis-identifies-distinct-t-cell-polarization-programs-and-a-biphasic-regulatory-response
#13
Darren J Lee, Janine Preble, Stacey Lee, C Stephen Foster, Andrew W Taylor
Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883938/pretreatment-of-activated-human-cd8-t-cells-with-il-12-leads-to-enhanced-tcr-induced-signaling-and-cytokine-production
#14
Aldo Vacaflores, Samantha N Freedman, Nicole M Chapman, Jon C D Houtman
During the immune response to pathogens and autoantigens, CD8T cells are exposed to numerous inflammatory agents including the cytokine IL-12. Previous studies have focused on how IL-12 regulates T cell functions when present during or after the activation of the T cell receptor (TCR). However, recent studies suggest that prior exposure to IL-12 also alters the TCR responsiveness of murine T cells. Whether similar phenomena occur in human activated CD8T cells and the mechanisms mediating these effects remain unexplored...
November 21, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27883081/v-d-j-recombination-process-and-the-pre-b-to-immature-b-cells-transition-are-altered-in-fanca-mice
#15
Thuy Vy Nguyen, Patrycja Pawlikowska, Virginie Firlej, Filippo Rosselli, Saïd Aoufouchi
B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-joining pathway...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881117/novel-prokaryotic-expression-of-thioredoxin-fused-insulinoma-associated-protein-tyrosine-phosphatase-2-ia-2-its-characterization-and-immunodiagnostic-application
#16
Luciano Lucas Guerra, Natalia Inés Faccinetti, Aldana Trabucchi, Bruno David Rovitto, Adriana Victoria Sabljic, Edgardo Poskus, Ruben Francisco Iacono, Silvina Noemí Valdez
BACKGROUND: The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A)...
November 24, 2016: BMC Biotechnology
https://www.readbyqxmd.com/read/27876151/identification-of-an-epitope-from-adenine-nucleotide-translocator-1-that-induces-inflammation-in-heart-in-a-j-mice
#17
Rakesh H Basavalingappa, Chandirasegaran Massilamany, Bharathi Krishnan, Arunakumar Gangaplara, Guobin Kang, Vahid Khalilzad-Sharghi, Zhongji Han, Shadi Othman, Qingsheng Li, Jean-Jack Riethoven, Raymond A Sobel, David Steffen, Jay Reddy
Heart failure, a leading cause of death in humans, can emanate from myocarditis. Although most individuals with myocarditis recover spontaneously, some develop chronic dilated cardiomyopathy. Myocarditis may result from both infectious and noninfectious causes, including autoimmune responses to cardiac antigens. In support of this notion, intracellular cardiac antigens, like cardiac myosin heavy chain-α, cardiac troponin-I, and adenine nucleotide translocator 1 (ANT1), have been identified as autoantigens in cardiac autoimmunity...
December 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27872147/primary-human-and-rat-beta-cells-release-the-intracellular-autoantigens-gad65-ia-2-and-proinsulin-in-exosomes-together-with-cytokine-induced-enhancers-of-immunity
#18
Chiara Cianciaruso, Edward A Phelps, Miriella Pasquier, Romain Hamelin, Davide Demurtas, Mohamed Alibashe Ahmed, Lorenzo Piemonti, Sachiko Hirosue, Melody A Swartz, Michele De Palma, Jeffrey A Hubbell, Steinunn Baekkeskov
The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellular membrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these proteins can initiate autoimmunity. We found that rat and human pancreatic islets release the intracellular β-cell autoantigens in human T1D, GAD65, IA-2 and proinsulin, in exosomes, which are taken up by and activate dendritic cells. Accordingly, anchoring of GAD65 to exosome-mimetic liposomes strongly boosted antigen presentation and T cell activation in the context of the human type 1 diabetes susceptibility haplotype HLA-DR4...
November 21, 2016: Diabetes
https://www.readbyqxmd.com/read/27871892/pso-p27-a-serpinb3-b4-derived-protein-is-most-likely-a-common-autoantigen-in-chronic-inflammatory-diseases
#19
Ole-Jan Iversen, Hilde Lysvand, Geir Slupphaug
Autoimmune diseases are characterized by chronic inflammatory reactions localized to an organ or organ-system. They are caused by loss of immunologic tolerance toward self-antigens, causing formation of autoantibodies that mistakenly attack their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in which the underlying molecular mechanisms remain elusive. In this review, we present evidence accumulated through more than three decades that the serpin-derived protein Pso p27 is an autoantigen in psoriasis and probably also in other chronic inflammatory diseases...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27870550/clinical-and-immunological-characteristics-of-autoimmune-addison-s-disease-a-nationwide-swedish-multicenter-study
#20
Frida Dalin, Gabriel Nordling Eriksson, Per Dahlqvist, Åsa Hallgren, Jeanette Wahlberg, Olov Ekwall, Stefan Söderberg, Johan Rönnelid, Per Olcén, Ola Winqvist, Sergiu-Bogdan Catrina, Berit Kriström, Maria Laudius, Magnus Isaksson, Maria Halldin Stenlid, Jan Gustafsson, Gennet Gebre-Medhin, Sigridur Björnsdottir, Annika Janson, Anna-Karin Åkerman, Jan Åman, Karel Duchen, Ragnhildur Bergthorsdottir, Gudmundur Johannsson, Emma Lindskog, Mona Landin-Olsson, Maria Elfving, Erik Waldenström, Anna-Lena Hulting, Olle Kämpe, Sophie Bensing
CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality. OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors. DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014...
November 21, 2016: Journal of Clinical Endocrinology and Metabolism
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