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Catalina Burbano, Juan Villar-Vesga, Janine Orejuela, Carlos Muñoz, Adriana Vanegas, Gloria Vásquez, Mauricio Rojas, Diana Castaño
Microparticles (MPs) are vesicles derived from the plasma membrane of different cells, are considered a source of circulating autoantigens, and can form immune complexes (MPs-ICs). The number of MPs and MPs-ICs increases in patients with systemic lupus erythematosus (SLE). MPs activate myeloid cells by inducing IL-6 and TNF-α in both SLE and other diseases. Therefore, we propose that the recognition of MPs-ICs by monocytes rather that MPs may define their phenotype and contribute to the inflammatory process in patients with SLE...
2018: Frontiers in Immunology
Xin Li, Haixia Li, Qiongdan Hu, Jinfei Lin, Qiong Zhang, Yao Li, Juan Li, Tao Chen, Qiong Zhang, Yurong Qiu
Systemic lupus erythematosus (SLE) is a common autoimmune disease, which features the secretion of antibodies directed against autoantigens in vivo. In the present study, a peptide microarray was developed to detect the epitopes recognized by autoantibodies in patients with SLE for an effective method of diagnosis. SLE‑associated epitopes in 14 autoantigens were predicted using the antigenic epitope prediction software DNA star. Peptides were synthesized based on the predicted antigenic epitopes and immobilized on a slide surface and developed into a peptide microarray...
March 9, 2018: Molecular Medicine Reports
Lu Li, Hai-Dong Fu
Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE). Reactive oxygen species derived from the nicotinamide adenine dinucleotide phosphate oxidase pathway or mitochondrial DNA pathway play a key role in the primary stage of NETs formation. The exposure or delayed degradation of abundant autoantigens, such as double-strand DNA, caused by abnormal activation of neutrophils can induce autoantibody to form immune complexes that deposit in local tissues and then induce the plasmacytoid dendritic cells to secrete the interferon alpha and other inflammatory factors...
March 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Eleni Theocharidou, Michael A Heneghan
Autoimmune hepatitis occurs in genetically susceptible individuals as a result of loss of immunological tolerance to hepatic autoantigens that can be precipitated by environmental triggers. The clinical manifestation is usually insidious but can be also acute with liver failure. The diagnosis is made on the basis of antibody positivity, elevated immunoglobulin G levels and interface hepatitis on liver histology. Induction of remission is achieved with high-dose steroids in the majority of cases, and maintenance of remission with azathioprine...
March 2, 2018: British Journal of Hospital Medicine
Xinhua Yu, Frank Petersen
Autoimmune disorders are characterized by a loss of immune tolerance and consequent autoimmunity-mediated disease manifestation. Experimental models are invaluable research tools helping us to understand disease pathogenesis and to search for novel therapeutics. Animal models of autoimmune diseases consist of two groups, spontaneous and induced models. In this review article, we focus on the induced models of autoimmune diseases. Due to the complex nature of autoimmune disorders, many strategies have been applied for the induction of corresponding experimental models in animals like monkeys, rabbits, rats, and mice...
March 8, 2018: Autoimmunity Reviews
Isabel Lopez-Oliva, Akshay D Paropkari, Shweta Saraswat, Stefan Serban, Zehra Yonel, Praveen Sharma, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa M Grant, Purnima S Kumar
OBJECTIVES: Studies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. Therefore, the present investigation sought to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with and without RA. METHODS: Subgingival plaque was collected from was collected periodontally healthy individuals (22 with and 19 without RA), and 16S gene sequenced on the Ilumina MiSeq platform...
March 7, 2018: Arthritis & Rheumatology
Marlena Godlewska, Wanda Krasuska, Barbara Czarnocka
Thyroid peroxidase (TPO) is an enzyme and autoantigen expressed in thyroid and breast tissues. Thyroid TPO undergoes a complex maturation process however, nothing is known about post-translational modifications of breast-expressed TPO. In this study, we have investigated the biochemical properties of TPO expressed in normal and cancerous human breast tissues, and the maturation process and antigenicity of TPO present in a panel of human breast tissue-derived cell lines. We found that the molecular weight of breast TPO was slightly lower than that of thyroid TPO due to decreased glycosylation and as suggest results of Western blot also shorter amino acid chain...
2018: PloS One
David P Funda, Jaroslav Goliáš, Tomáš Hudcovic, Hana Kozáková, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic DCs (tolDCs) are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D). T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65), that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD)-severe combined immunodeficiency (NOD-SCID) recipients...
2018: Frontiers in Immunology
Urs Christen, Edith Hintermann
Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are serious autoimmune liver diseases that are characterized by a progressive destruction of the liver parenchyma and/or the hepatic bile ducts and the development of chronic fibrosis. Left untreated autoimmune liver diseases are often life-threatening, and patients require a liver transplantation to survive. Thus, an early and reliable diagnosis is paramount for the initiation of a proper therapy with immunosuppressive and/or anticholelithic drugs...
2018: Frontiers in Immunology
Jonas Blomberg, Carl-Gerhard Gottfries, Amal Elfaitouri, Muhammad Rizwan, Anders Rosén
Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection...
2018: Frontiers in Immunology
Maria Diedrichs-Möhring, Ulrike Kaufmann, Gerhild Wildner
Autoimmune diseases usually follow a relapsing-remitting or a chronic progressive course. To understand the underlying immunopathogenesis we investigated experimental Lewis rat models displaying both disease types, which were only dependent on the autoantigen peptide used for immunization. Retinal S-Antigen-peptide PDSAg induces chronic, monophasic disease, whilst interphotoreceptor retinoid-binding protein (IRBP)-peptide R14 causes a spontaneously relapsing-remitting course. R14-mediated uveitis can be re-induced by immunization; PDSAg-induced disease is even preventable by prior CFA-injection...
February 26, 2018: Progress in Retinal and Eye Research
Fang-Yuan Gong, Zheng Gong, Cui-Cui Duo, Jun Wang, Chao Hong, Xiao-Ming Gao
Calreticulin (CRT), a luminal resident calcium-binding glycoprotein of the cell, is a tumor-associated antigen involved in tumorigenesis and also an autoantigen targeted by autoantibodies found in patients with various autoimmune diseases. We have previously shown that prokaryotically expressed recombinant murine CRT (rCRT) exhibits strong stimulatory activities against monocytes/macrophages in vitro and potent immunogenicity in vivo, which is partially attributable to self-oligomerization of soluble rCRT. However, even in oligomerized form native CRT (nCRT) isolated from mouse liver is much less active than rCRT, arguing against the possibility that self-oligomerization alone would license potent pro-inflammatory properties to nCRT...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Silvia Rodriguez-Fernandez, Irma Pujol-Autonell, Ferran Brianso, David Perna-Barrull, Mary Cano-Sarabia, Sonia Garcia-Jimeno, Adrian Villalba, Alex Sanchez, Eva Aguilera, Federico Vazquez, Joan Verdaguer, Daniel Maspoch, Marta Vives-Pi
Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC) generation...
2018: Frontiers in Immunology
A Lounici Boudiaf, D Bouziane, M Smara, Y Meddour, E M Haffaf, B Oudjit, S Chaib Mamouzi, S Aouichat Bouguerra
BACKGROUND: The zinc transporter 8 (ZnT8) is an islet β-cell secretory granule membrane protein coded by the SLC30A8 gene, identified as a novel autoantigen in human type 1 diabetes (T1D). As no data of ZnT8ab in Algerian patients have been reported, we aim to evaluate the prevalence of ZnT8ab in young Algerians with T1D and determine whether ZnT8ab could be a better diagnostic tool to replace the other conventional autoantibodies detected in patients with type 1 diabetes. For this purpose, we evaluated the prevalence of islets cells antibodies (ICA), glutamic acid decarboxylase (GAD), islet antigen type 2 (IA2), insulin (IA) autoantibodies (ab) and for the first time in Algeria, the zinc transporter 8 (ZnT8) in young Algerian patients with type 1 diabetes...
February 24, 2018: Current Research in Translational Medicine
Emma C de Moel, Veerle F A M Derksen, Gerrie Stoeken, Leendert A Trouw, Holger Bang, Robbert J Goekoop, Irene Speyer, Tom W J Huizinga, Cornelia F Allaart, René E M Toes, Diane van der Woude
BACKGROUND: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. METHODS: In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs))...
February 26, 2018: Arthritis Research & Therapy
Zhuochun Huang, Qian Niu, Bin Yang, Junlong Zhang, Min Yang, Huan Xu, Bei Cai, Jing Hu, Yongkang Wu, Lanlan Wang
HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3' UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression...
February 23, 2018: Clinical Rheumatology
Mayumi Kamaguchi, Hiroaki Iwata, Inkin Ujiie, Hideyuki Ujiie, Jun Sato, Yoshimasa Kitagawa, Hiroshi Shimizu
Mucous membrane pemphigoid (MMP) is a rare organ-specific autoimmune subepithelial blistering disease with predominantly mucosal erosions, most frequently affecting the gingiva. Erosions in the oral cavity usually result in markedly decreased quality of life. The major autoantigens are BP180 and laminin332, which are components of basement membrane proteins in the skin and mucosa. Diagnosis is usually difficult due to histological destruction of the tissue and low autoantibody titers. In this study, we evaluated the diagnostic value of direct immunofluorescence (DIF) using non-lesional buccal mucosa in seven cases of MMP...
2018: Frontiers in Medicine
Jeremy J Racine, Isabel Stewart, Jeremy Ratiu, Greg Christianson, Emily Lowell, Kelsay Helm, Jennifer Allocco, Richard S Maser, Yi-Guang Chen, Cathleen M Lutz, Derry Roopenian, Jennifer Schloss, Teresa P DiLorenzo, David V Serreze
Improved mouse models for type 1 diabetes (T1D) therapy development are needed. T1D susceptibility is restored to normally resistant NOD.β2m-/- mice transgenically expressing human disease associated HLA-A*02:01 or HLA-B*39:06 class I molecules in place of their murine counterparts. T1D is dependent on pathogenic CD8+ T-cell responses mediated by these human class I variants. NOD.β2m-/- -A2.1 mice were previously used to identify β-cell autoantigens presented by this human class I variant to pathogenic CD8+ T-cells, and for testing therapies to attenuate such effectors...
February 22, 2018: Diabetes
Hui Fang, Shuai Shao, Man Jiang, Erle Dang, Shengxian Shen, Jieyu Zhang, Pei Qiao, Caixia Li, Gang Wang
Bullous pemphigoid is an autoimmune inflammatory disorder characterised by the presence of autoantibodies against bullous pemphigoid autoantigens, leading to dermal-epidermal separation with consequent blister formation. However, whether and how the components of blister fluid exacerbate the progression of bullous pemphigoid is unclear. Exosomes are nanometre-sized vesicles released from cells into the body fluid, where they can transmit signals throughout the body. In the present study, we isolated and characterised exosomes from the blister fluids of patients with bullous pemphigoid, evaluated their proinflammatory role, and identified the underlying molecular mechanisms...
February 22, 2018: Journal of Pathology
Magdalena Sroka, Harini Bagavant, Indranil Biswas, Abigail Ballard, Umesh S Deshmukh
OBJECTIVES: The structural domains of Ro52, termed the RING, B-box, coiled coil (CC) and B30.2/SPRY are targets of anti-Ro52 in multiple autoimmune disorders. In Sjögren's syndrome patients, the presence of anti-Ro52 is associated with higher disease severity, and in mice, they induce salivary gland hypofunction. This study was undertaken to investigate whether immune responses against different domains of Ro52, influences salivary gland disease in mice. METHODS: Female NZM2758 mice were immunised with Ro52 domains expressed as recombinant fusion proteins with maltose binding protein (MBP) [MBP-RING-B-box, MBP-CC, MBP-CC(ΔC19), MBP-B30...
January 31, 2018: Clinical and Experimental Rheumatology
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